Anti-cancer green bionanomaterials: present status and future prospects

Figures & data

Figure 1. Biological synthesis and applications of metal NPs in biomedical and environmental fields (Adapted with permission from Singh et al. (12)).

Figure 2. Schematic mechanism of microbial-mediated synthesis of metal nanoparticles (Adapted with permission from Salunke et al. (11)).

Figure 3. Plant-mediated mechanism of biogenic silver nanoparticles’ (AgNPs’) production: a step forward for cancer nanomedicine (Adapted with permission from Ovais et al. (21)).

Table 1. Phyto-sources for synthesis of bionanoparticles and their anticancer activity in various cell lines for the past 5 years.

Plant	Part used	Nanoparticle type	Size (nm)	Morphology	Anticancer activity (In vitro model)^a	Dose (µg/well)	Exposure time	Major outcome	Reference
Acalypha indica	Leaf	CuO	26–30 nm	Spherical	MCF-7	6.5–100 μg/mL	48 h	IC50: 56.16 μg/mL	Sivaraj and colleagues (32)
Achillea biebersteinii	Leaf	Ag	10–40 nm	Spherical and pentagonal	MCF-7	15–100 µg/mL	24 h	IC50: 20 µg/mL	Baharara et al. (153)
Adenium obesum	Leaf	Ag	10–30 nm	Spherical	MCF-7	100–600 µg/mL	24 h	IC50: 217 µg/mL	Farah et al. (154)
Ailanthus excelsa	Leaf	Ag	22–30 nm	Spherical	MCF-7	50–150 µg/mL	24 h	IC50:265.579 µg/mL	Vinmathi and JACOB (155)
Albizia adianthifolia	Leaf	Ag	4–35 nm	Spherical	A549 and PLs	10 and 50 μg/mL	6 h	Low toxicity at 10μl/mL, but significant toxicity at 50μl/mL in A549 No toxicity in PLs	Gengan and colleagues (34)
Aloe vera	Leaf	Ag	70.7–192.02 nm	Spherical	PBMCs	0.0025–0.04 mg/mL	48 h	IC50: ≤0.0025 mg/mL	Tippayawat and colleagues (82)
Alternanthera sessilis	Leaf	Ag	30–50 nm	Spherical	PC3	1.56- 25μl/mL	48 h	IC50: 6.85 μg/mL	Firdhouse and Lalitha (156)
Alternathera tenella	Leaf	Ag	∼48 nm	Spherical	MCF-7	25–100 µg/mL	24 h	IC50: 42.5 µg/mL	Sathishkumar et al. (157)
Andean Mora (Rubus glaucus Benth.)	Leaf	Ag	12–50 nm	Quasi-spherical	HepG2	0.01–1.0 µM	2 h	No toxicity observed	Kumar and colleagues (65)
Annona squamosa	Peel	SnO2	Average size:27.5 nm	Spherical	HepG2	1–500 μg/mL	2 h	IC50:148 μg/mL	Roopan and colleagues (66)
Antigonon letopus Hook. and Arn.	Aerial part	Au	13–28 nm	Spherical with few triangular shapes	MCF-7	31.25–1000 µg/mL	48 h	IC50: 257.8 µg/mL	Balasubramani et al. (158)
Apple (Malus domestica)	Fruit	Ag	10–40 nm	Spherical	MCF-7	10–100 µg/mL	24 and 48 h	No toxicity at ≤ 70 µg/mL after 24 h of incubation Significant toxicity at ≥10 µg/mL after 48 h of incubation	Lokina and colleagues (9)
Areca catechu	Nut	Au	22.2 nm	Spherical	HeLa	6.25–100 µg/mL	24 h	IC50: 25.17 µg/mL	Rajan and colleagues (37)
Argemon maxcana	Leaf	Ag	2–6 nm	Spherical	SiHa	25–100 µg/mL	72 h	IC50:>50 µg/mL Significant toxicity at 100 µg/mL	Jha and Prasad (63)
Artemisia marschalliana Sprengel	Aerial part	Ag	5–50 nm	Spherical	AGS	3.125–100 µg/mL	24 h	IC50: 21.05 µg/mL in AGS	Salehi and colleagues (44)
Azadirachta indica	Leaf	Au	≤121.7 nm	Spherical, hexagonal and triangular	HeLa and MDCK	0.1–0.25mM	48 h	No toxicity	Dharmatti and colleagues (86)
Azadirachta indica (neem)	Leaf	Ag	94 nm	Spherical	HDFa and NCI-H460	0–240ppm	24 h	Very high toxicity at 240 ppm in NCI-H460, but no toxicity in normal HDFa	Kummara and colleagues (39)
Bambusa arubdinacea (Ba) and Bambusa nutans (Bn)	Leaf	Ag	30–90 nm	Spherical	PC3 and Vero cells	10–100 µg/mL	48 h	IC50: 73.57 µg/mL for BaAgNP in PC3 IC50: 84.88 µg/mL for BnAgNP in PC3 IC50: 93.58 µg/mL for BaAgNP in Vero IC50: 96.41 µg/mL for BnAgNP in Vero	Kalaiarasi et al. (159)
Borago officinalis	Leaf	Ag	30–80 nm	Spherical, hexagonal, and irregular	RAW 264.7, A549 and HeLa	1–10 µg/mL	24 h	No significant toxicity in RAW 264.7, Significant toxicity in A549 at 10 µg/mL and HeLa at 5 µg/mL	Singh and colleagues (35)
Broccoli	Whole plant	Cu	∼4.8 nm	Spherical	PC-3	0.5–1.5µM	2 h	No toxicity	Prasad and colleagues (52)
Broccoli florets (Brassica Oleracea L.var. Italica)	Aerial part	Ag	40- 50 nm	Spherical	MCF-7	50–150 µg/mL	24 h	IC50: 121.56μg/mL	Caroling et al. (160)
Bruguiera cylindrica	Leaf	Ag	9–24 nm	Hexagonal	MCF-7	50, 100 µg/mL	12, 24, 36 h	IC50: 100 µg/mL after 12 h of incubation 90% toxicity at 100 µg/mL after 36 h of incubation	Bhuvaneswari et al. (161)
Butea monosperma	Leaf	Ag and Au	20–80 nm	Mainly spherical but few rods, irregular and hexagonal	B16F10, MCF-7, HNGC2, A549, HUVEC and ECV-304	0.3–2.5µM	24, 48 h	No toxicity	Patra and colleagues (55)
Cajanus cajan	Seed coat	Au	9–41 nm	Spherical	HepG2 and vero cells	2–10 µg/mL in HepG2 10–320 µg/mL in vero cells	24 h	IC50:6 µg/mL in HepG2
IC50:246 µg/mL in vero cells	Ashokkumar et al. (162)
Calotropis procera L.	Latex	Cu	5–30 nm	Spherical	HeLa, A549 and BHK21	20–160 μM	24 h	No toxicity	Harne and colleagues (89)
Cassia fistula	Flower	Ag	21–30 nm	Spherical	MCF-7 and Vero cells	7.8–1000 µg/mL	24 h	IC50: 7.19 µg/mL in MCF-7 IC50: 66.34 µg/mL in Vero cell line	Remya et al. (163)
Cassytha filiformis	Whole plant	Ag	16–66 nm	Spherical	HCT116	0.1–10 μg/mL	24 h	IC50:0.5 mg/mL	Jena and colleagues (36)
Cauliflower floret (Brassica Oleracea. var. botrytis. l)	Aerial part	Ag	40–50 nm	Spherical	MCF-7	50–150 μg/mL	24 h	Moderate (40.24%) toxicity at 150 μg/mL IC50: 190.501 µg/mL	Ranjitham et al. (164)
Chlorella vulgaris (Algae)	Whole cell	Ag	6.5–13.5 nm (Average size: 9 nm)	Spherical	HepG2	2.35- 300 µg/mL	24 and 48 h	≥4.7 µg/mL significant toxicity after 24 h and 48h	Ebrahiminezhad et al. (165)
chrysanthemum indicum	Flower	Ag	37.71–71.99 nm	Spherical	3T3	25 and 50 µg/mL	24 h	No toxicity at 25 µg/mL, but toxic at 50 µg/mL	Arokiyaraj and colleagues (83)
Chrysophyllum oliviforme (Satin leaf)	Leaf	Ag	25 nm	Flower	HeLa	6.25–100 µg/mL	48 h	IC50: 40.365 µg/mL	Anju Varghese R (166)
Cissus quadrangularis	Stem	Ag	5–30 nm	Spherical	HEp 2 and Vero cells	20–160 μg	4 h	IC50:64μg in HEp 2 IC50:90μg in Vero	Renugadevi and colleagues (68)
Clerodendron serratum	Leaf	Ag	5–30 nm	Spherical	EAC	5–60 µg/mL	24 h	IC50∼40 µg/mL	Raman and colleagues (57)
Cucurbita maxima, Moringa oleifera and Acorus calamus	C. maxima (petal), M. oleifera (leaf) and A. calamus (rhizome)	Ag	30–70 nm	Spherical and cuboidal	A431	10–150 µg/mL	24 h	IC50:82.39 ± 3.1 µg/mL in AgNPs synthesized from C. maxima IC50: 83.57 ± 3.9 µg/mL in AgNPs synthesized from M. oleifera IC50: 78.58 ± 2.7 µg/mL in AgNPs synthesized from A. calamus	Nayak and colleagues (62)
Cymodocea serrulata	Aerial part	Ag	17–29 nm	Spherical	HeLa and Vero cells	10–100 µg/mL	48 h	IC50: 34.5 µg/mL in Hela IC50:61.24 µg/mL in Vero cell	Chanthini et al. (167)
Cymodocea serrulata	Leaf	Ag	5–25 nm	Spherical	A549	10–250 µg/mL	36 h	IC50: 100 µg/mL	Palaniappan et al. (168)
Datura inoxia	Leaf	Ag	30–60 nm	–	MCF-7	10–80 µg/mL	24 h	IC50: 20 μg/mL	Gajendran et al. (169)
Delonix regia	Petal	ZnO	65–184 nm	Spherical	A549	5–20 µg/mL	1–5 days	Very low toxicity after 1 day IC50∼20 µg/mL after 2 day Low toxicity at ≤10 µg/mL after 5 days	Abbasi et al. (170)
Dendropanax morbifera	Leaf	Ag and Au	Ag:100–150 nm Au: 10–20 nm	Polygon and hexagon	HaCaT and A549	1–100 µg/mL	48 h	No toxicity of AuNPs at 100 µg/mL in HaCaT and A549, Low toxicity of AgNPs at 100 µg/mL in HaCaT, No toxicity of AgNPs at 10 µg/mL, but significant toxicity at 100 µg/mL in A549	Wang and colleagues (77)
Dimocarpus Longan Lour.	Peel	Ag	9–32 nm	Spherical	PC-3	2–30 μg/mL	72 h	IC50: 5–10 µg/mL	He and colleagues (53)
Dioscorea bulbifera	Tuber	Pt, Pd, Pt–Pd	PtNPs:2–5 nm PdNPs:10–20 nm Pt–PdNPs:20–25 nm	PtNPs: spherical PdNPs: spherical and blunt ended cubes Pt–PdNPs: irregular	HeLa	10 µg/mL	48 h	Cytotoxic effect at 10 µg/mL: PtNPs (12.6%), PdNPs (33.15%), and Pt–PdNPs (74.25%)	Ghosh et al. (171)
Dracocephalum kotschyi	Leaf	Au	11 nm	Spherical	K562 and HeLa	62.5–500 µg/mL	24, 48 and 72 h	IC50: 196.32 µg/mL in K562 and IC50: 152.16 µg/mL in Hela	Dorosti and Jamshidi (61)
Ecklonia cava (marine brown alga)	Seaweed	Au	20–50 nm	Spherical and triangular	HaCaT	10–50 µg/mL	24,48, 72 h	No toxicity	Venkatesan and colleagues (76)
Eclipta alba	Leaf	Ag	310–400 nm	Cubic	RAW254.7, MCF-7 and Caco-2	0.5–50 µM	48 h	IC50: 5 µM in MCF-7 IC50:7 µM in RAW254.7 IC50: 10 µM in Caco-2	Premasudha and colleagues (49)
Erythrina indica lam	Root	Ag	20–118 nm	Spherical	MCF-7 and HepG2	0.625–25 µg/mL	24 h	IC50: 2.5 µg/mL in HEP G2 IC50∼8 µg/mL in MCF-7	Sre et al. (172)
Eucalyptus	Leaf	Ag	30–70 nm	–	AGS, MRC-5	3–100 µg/mL	24,48,72 h	IC50: 9.01, 6.31, 3.99 µg/mL in AGS after 24, 48 and 72 h of incubation, respectively. IC50: 35.44, 30.13, 21.28 µg/mL in MRC-5 after 24, 48 and 72 h of incubation, respectively.	Rashmezad and colleagues (45)
Ficus benghalensis Azadirachta indica	Bark	Ag	∼40 nm and ∼50 nm	Spherical	MG-63	20–200 μg/mL	48 h	IC50: 81.8 ± 2.6 μg/mL for Ag from A. indica IC50:75.5 ± 2.4 μg/mL for Ag from F. benghalensis	Nayak and colleagues (42)
Ficus religiosa	Bark	Au	20–30 nm	Spherical	HEK 293	10–200 μM	24 h	No toxicity	Wani K (78)
Genipa americana L.	Fruit	Au	30.4 ± 14.9 nm	Spherical	A-549 and Hela	0.01–20µM	48 h	No toxicity observed	Kumar et al. (173)
Haliclona exigua (marine sponge)	Sponge	Ag	0.078–5 μg/mL	Flower like	KB	100 to 120 nm	48 h	IC50: 0.6 µg/mL	Inbakandan and colleagues (72)
Helianthus Annuus L.	Sunflower oil	Ag	Spherical: ∼10 nm Hexagonal:40–50 nm	Spherical and hexagonal	A549	10–100 µg/mL	24 h	IC50∼65 µg/mL	Thakore et al. (174)
Helicteres isora	Stem bark	Ag	16–95 nm	Spherical	KB	0–200 µg/mL	24 h	IC50: 70 µg/mL	Bhakya and colleagues (73)
Hibiscus sabdariffa	leaf and stem	Au	10–60 nm	Near spherical	U87 and HEK 293	0–2.5 ng/mL	48 h	IC50∼1.5 ng/mL and high toxicity at 2 ng/mL in U87 and little toxicity in HEK 293	Mishra and colleagues (40)
Impatiens balsamina	Flower	Ag	Average size: 15 nm	Spherical	U937, COLO205, B16F10, HepG2, HeLa	25–200 µg/mL	24 h	IC50:84.17 ± 2.13 µg/mL in U-87 IC50:65.40 ± 2.41 µg/mL in COLO205 IC50:196.5 ± 4.19 µg/mL in B16F10 IC50:95.52 ± 4.08 µg/mL in HepG2 IC50:93.27 ± 2.53 µg/mL in HeLa	Nalavothula R (54)
Iresine herbstii	Leaf	Ag	44–64 nm	Cubical	HeLa	25–300 μg/mL	3 h	IC50:51 μg/mL	Dipankar and Murugan (175)
Justicia adhatoda	Leaf	Ag	11–20 nm	Spherical	HeLa	10–80 µg/mL	4 h	IC50:55 µg/mL	Kudle et al. (176)
Lavandula vera	Leaf	Zn	30–80 nm	Spherical	A549, MCF-7, HT-29, and Caco-2	10–160 µg/mL	24 h	IC50: 22.3 ± 1.1 µg/mL in A549 IC50: 86 ± 3.7 µg/mL in MCF-7 IC50: 10.9 ± 0.5 µg/mL in HT-29 IC50: 56.2 ± 2.8 µg/mL in Caco-2	Salari and colleagues (47)
Mangifera indica Linn	Peel	Au	6.03 ± 2.77–18.01 ± 3.67 nm	Quasi-spherical	CV-1 and WI-38	10–160 μg/mL	24 h	No toxicity	Yang and colleagues (87)
Mimosa pudica	Leaf	Au	12 nm	Spherical	MDA-MB-231, MCF-7 and HMEC	2–10 μg/mL for MDA-MB-231 & MCF-7 5–80 μg/mL for HMEC	24 and 48 h	IC50:4 µg/mL in MDA-MB-231 after 48 h of incubation IC50:6 µg/mL in MCF-7 after 48 h of incubation IC50 did not observed after 24 h no significant toxicity in HMEC	KS and colleagues (33)
Momordica charantia	Leaf	Ag	∼91.63 nm	Spherical	MCF-7	12–100 µg/mL	24 h	IC50: not exactly mentioned in the text, but between 50–100 µg/mL	Gandhiraj V (177)
Momordica cymbalaria	Fruit	Ag	Average size: 15.5 nm	Spherical	Rat L6	20–100 µg/mL	24–48 h	IC50∼20 µg/mL	Swamy and colleagues (85)
Morinda citrifolia	Root	Ag	30–55 nm	Spherical	HeLa	0.1–100 μg/mL	24 h	Highly significant toxicity at 100 μg/mL	Suman et al. (178)
Moringa oleifera	Flower	Pd	10–50 nm and 2–18 nm	Spherical	A549 and human normal peripheral lymphocytes cells	10 μg/mL and 50 μg/mL	6 h	Significantly cytotoxic to A549 cells and no toxicity in normal peripheral lymphocytes	Anand and colleagues (95)
Musa paradisiaca (banana)	Stem of banana	Au	Average size: 30 nm	Spherical	MCF-7 and HEK-293	10–100 nM	24 h	IC50:>80 nM in MCF-7 No toxicity at 60 nM in HEK-293, but low toxicity above 60 nM	Arunkumar and colleagues (88)
Oak fruit hull (Jaft)	Fruit	Ag	Average size: 40 nm	Spherical	MCF-7 and human blood mononuclear cells	0.02–50 µg/mL	24 h	IC50: 50 µg/mL (AgNPs in purified water) in MCF-7 IC50:0.04 µg/mL (AgNPs in plant extract) in MCF-7 No toxicity in human blood mononuclear cells	Heydari and Rashidipour (99)
Origanum vulgare (Oregano)	Leaf	Ag	63–85 nm	Spherical	A549	10–500 μg/mL	36 h	IC50:100 µg/mL	Sankar et al. (179)
Padina gymnospora (marine Macroalgae)	Leaf	Au	Average size: 14.10 ± 1.5 nm	Spherical	HepG2, A549, and 3T3	5–80 nM	48 h	IC50: 51.9 nM in HepG2 IC50: 76.40 nM in A549 No toxicity in 3T3	Singh and colleagues (84)
Piper pedicellatum	Fruit	gold-reduced graphene oxide (Au-rGO) nanocomposite	8–15 nm	Pentagonal, hexagonal and spherical	PC3 and RWPE-1	10–50 µg/mL	–	IC50: 12.02 µg/mL in PC3 IC50: 25.1 µg/mL in RWPE-1	Saikia and colleagues (81)
Plumbago zeylanica, Semecarpus anacardium and Terminalia arjuna	Bark, root bark and nut, for P. zeylanica, S. anacardium and T. arjuna, respectively	Ag	80–98 nm, 60–95 nm and 34–70 nm for P. zeylanica, S. anacardium and T. arjuna, respectively	Spherical for P. zeylanica and T. arjuna Cubic for S. anacardium	HepG2, PC3 and Vero cells	1–100 μg/mL	48 h	IC50 of HepG2, PC3 and Vero cells: 70.97, 58.61, 96.41 μg/mL, respectively for P. zeylanica. IC50 of HepG2, PC3 and Vero cells: 83.86, 42.77, 10.04 μg/mL, respectively for S. anacardium. IC50 of HepG2, PC3 and Vero cells: 28.42, 41.78, 69.48 μg/mL, respectively for T. arjuna.	Prasannaraj and colleagues (79)
Potentilla fulgens	Root	Ag	10–15 nm	Spherical	MCF-7 and U-87	0–12 µg/mL	24 h	IC50:4.91 µg/mL in MCF-7 IC50:8.23 µg/mL in U-87	Mittal et al. (180)
Premna serratifolia L.	Leaf	Ag	16–32 nm, (Average size: 22.97 nm)	Cubic	Hepato-cancerous Swiss albino mice	500 mg/Kg in vivo	15 days (In vivo study in mice)	Significant anticancer effect to improve biochemical plasma factors to reach normal levels	Patra and colleagues (55)
Rheum rhabarbarum	Stem	Ag	60–80 nm	Spherical	HeLa	10–500 μg/mL	72 h	IC50: 28.5 μg/mL	Reddy et al. (181)
Rosa canina	Fruit	ZnO	≤ 50 nm	Spherical	A549	0.05–0.5 mg/mL	24 h	No significant toxic effect up to 0.1 mg/mL IC50∼0.25 mg/mL	Jafarirad et al. (182)
Rosa indica	Petal	Ag	23.52–60.83 nm	Spherical	HCT 15	5–60 µg/mL	24 h	IC50: ∼30 µg/mL	Manikandan and colleagues (50)
Rosa indica	Petal	Ag	23.52–60.83 nm	Spherical	HCT 15	5–60 µg/mL	24 h	IC50: ∼30 µg/mL	Manikandan and colleagues (50)
Rosmarinus officinalis	Leaf	Ag	Average size: 60 nm	Cubical	HL-60	1 mM, 2mM	6, 12, 24 h	No IC50 after 6h IC50: <2 mM after 12h 80% toxicity at 2 mM after 24h	Sulaiman and colleagues (60)
Sargassum Muticum (algae)	Whole cell	hyaluronan/ zinc oxide (HA/ZnO) nanocomposite	3–8 nm	Polygonal	PANC-1, CaOV-3, COLO205, and HL-60 and MRC-5	0–100 μg/mL	72 h	IC50 is 10.8 ± 0.3 μg/mL, 15.4 ± 1.2 μg/mL, 12.1 ± 0.9 μg/mL, and 6.25 ± 0.5 μg/mL for the PANC-1, CaOV-3, COLO-205, and HL-60 cells, respectively. No toxicity observed in MRC-5	Namvar and colleagues (41)
Sargassum longifolium	Seaweed	Ag	Average size: 30 nm	Cubical	HEp 2	3.9–1000 μg/mL	48 h	IC50: 62.5 µg/mL	Devi and colleagues (69)
Sargassum muticum	Seaweed	ZnO	50–100 nm	Hexagonal	4T1, CRL-1451, CT-26, WEHI-3B and 3T3	0–100 µg/mL	72 h	IC50:21.7 ± 1.3 µg/mL in 4T1 IC50:17.45 ± 1.1 µg/mL in CRL-1451, IC50:11.75 ± 0.8 µg/mL in CT-26, and IC50:5.6 ± 0.55 µg/mL in WEHI-3B, no toxicity in 3T3	Namvar and colleagues (56)
Sargassum muticum	Seaweed	Au	5.42 ± 1.18 nm	Spherical	CEM-ss, Jurkat, HL-60, K562 and normal human blood mononuclear cells	0–100 µg/mL	72 h	IC50:4.22 ± 1.12 µg/mL in K562 IC50:5.71 ± 1.4, 6 µg/mL in HL-60 IC50: 55 ± 0.9 µg/mL in Jurkat IC50: 7.29 ± 1.7 µg/mL in CEM-ss no toxicity in normal human blood mononuclear cells	Namvar and colleagues (58)
Sargassum muticum	Seaweed	Fe3O4	18 ± 4 nm	Cubic	Jurkat, MCF-7, HeLa and HepG2	–	72 h	IC50:23.83 ± 1.1 μg/mL in HepG2 IC50:18.75 ± 2.1 μg/mL in MCF-7 IC50:12.5 ± 1.7 μg/mL in HeLa IC50:6.4 ± 2.3 μg/mL in Jurkat	Namvar and colleagues (59)
Sargassum swartzii	Seaweed	Au	20–60 nm	Spherical and few hexagonal	HeLa	15.63–500 µg/mL	24 h	IC50: 41.10 µg/mL	Dhas et al. (183)
Sesbania grandiflor	Leaf	Ag	10–45 nm	Spherical	MCF-7	0–50 µg/mL	24 and 48 h	IC50: 20 µg/mL	Jeyaraj et al. (184)
Solanum muricatum	Leaf	Ag	20–80 nm	Irregular	HeLa	10–100 µg/mL	72 h	IC50: 37.5 µg/mL	Gorbe et al. (185)
Solanum trilobatum	Fruit	Ag	12.50–41.90 nm	Spherical and polygonal	MCF 7	5–50 µg/mL	24 h	IC50: >20 µg/mL	Ramar et al. (186)
star anise (Illicium verum)	Pod	Au	20–150 nm	Triangular and hexagonal	A549	10–200 nM	48 h	Low toxicity	Sathishkumar et al. (187)
star anise (Illicium verum)	Pod	Au	20–50 nm and 30–150 nm	Triangular and hexagonal	A549	10–200 nM	48 h	Low toxicity at 200 nM	Sathishkumar and colleagues (187)
Sterculia foetida L.	Seed	Ag	Average size: 6.9 ± 0.2 nm	Spherical	HeLa	1–16 µg/mL	24 h	IC50: >2 µg/mL Significant toxicity at 16 µg/mL (>90%)	Rajasekharreddy and Rani (188)
Styrax benzoin	Benzoin gum	Ag	12–38 nm	Spherical	Raw 264.7, Hela, A549 and HaCaT	1–5 µg/mL in Raw 264.7, Hela and A549. 1–10 µg/mL in HaCaT	24 h	≤2 µg/mL no significant toxicity in Raw 264.7, ≥1 µg/mL significant toxicity in Hela and A549, no significant cytotoxic up to 10 µg/mL in HaCaT	Du and colleagues (96)
Syzygium cumini	Fruit	Ag	5–20 nm	Spherical	DL	50–500 µg/mL	48 h	IC50∼100 μg/mL	Mittal and colleagues (64)
Syzygium samarangense	Leaf	Ag	–	Spherical	A549	50–200 µg/mL	24 h	IC50: 87.37 µg/mL	Thampi and Shalini (189)
Tabernaemontana divaricata	Flower	Au	100 nm	Nearly spherical	MCF-7 and Vero cells	25–75 μg/mL	24 h	75 μg/mL moderate toxicity in MCF-7 but little toxicity in Vero cell line	Raj and Khusro (80)
Taxus yunnanensis	Callus	Ag	6.4–27.2 nm	Spherical	SMMC-7721, LS174T, A549, MCF-7 and HL-7702	10–50 µg/mL	24 h	IC50: 27.75 µg/mL in SMMC-7721 IC50: 81.39 µg/mL in HL-7702 IC50: 40.3 µg/mL in A549 IC50: 42.2 µg/mL in MCF-7 IC50:27.75 µg/mL in LS174T	Xia and colleagues (46)
Torreya nucifera, Cinnamomum japonicum, and Nerium indicum	Leaf	Ag	8–42 nm, 4 35 nm, 4–38 nm	Spherical, pentagonal	3T3-L1	0.1 ng/mL–10 μg/mL	24 h	Low toxicity in AgNPs from T. nucifera and N. indicum, but moderate toxicity in AgNPs from C. japonicum	Kalpana and colleagues (90)
Turbinaria turbinata (marine algae)	Whole cell	Ag	8–16 nm	Spherical	EAC	42–98 µg/mL	–	99% toxicity at 98 µg/mL	Khalifa et al. (190)
Vigna radiata (green gram)	Seed	Lanthanum	–	Spherical	Mg-63	12.5–200 µg/mL	48 h	IC50: 200 µg/mL	Chatterjee A (43)
Vigna radiata (green gram)	Seed	Titanium dioxide	–	–	Mg-63	12.5–200 µg/mL	48 h	IC50: 200 µg/mL	Chatterjee et al. (191)
Vitex negundo L.	Leaf	Ag	5–49 nm	Spherical	HCT15	10–100 μg/mL	48 h	IC50: 20 μg/mL	Prabhu and colleagues (51)
Zataria multiflora	Leaf	Au	10–50 nm (Average size: 20.52 nm)	Different shapes; pentagon, triangular, undefined shapes	HeLa and BMSCs	0–400 µg/mL	48 h	Significant toxicity at 400 µg/mL in Hela cell line (IC50:100 µg/mL). IC50: 300 µg/mL in BMSCs:	Baharara and colleagues (101)
Zingiber zerumbet	Rhizome	ZnO–Ag nanocomposite	23 nm	Spherical	Vero cells	0–300 µg/mL	24 h	No toxicity at ≤100 µg/mL but at higher concentration toxicity gradually increased	Azizi et al. (192)

^aCancer and normal Cell Lines: HeLa (human cervical cancer), HepG2 (hepatic cancer), MDA-MB-231 and MCF-7 (human breast adenocarcinoma), PC-3 (human prostate carcinoma), KB (human oral cancer), A549 (human lung adenocarcinoma), HCT116 (human colon colorectal carcinoma), EAC, NCI-H460 (non-small cell lung cancer), U87 (glioblastoma multiforme cell), PANC-1 (pancreatic adenocarcinoma), CaOV-3 (ovarian adenocarcinoma), COLO205 (colonic adenocarcinoma), HL-60 (acute promyelocytic leukemia), MG-63 (osteosarcoma cell), AGS (human gastric carcinoma), SMMC-7721 (human hepatoma cells), LS174T (human colon adenocarcinoma cell), HT-29 (human colorectal adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), HCT 15 (human colon adenocarcinoma), U937 (human histiocytic lymphoma cell), B16F10 (mouse melanoma), 4T1 (mouse breast cancer), CRL-1451 (mouse lung adenocarcinoma), WEHI-3B (Mouse leukemia), CEM-ss (human T acute lymphoblastic leukemia), Jurkat (human T acute lymphoblastic leukemia), K562 (human chronic myelogenous leukemia), A431 (human vulvar squamous cell carcinoma), HNGC-2 (human adult glioma tissue), ECV-304 (human urinary bladder carcinoma), RAW254.7 (mouse leukemia), SiHa (human cervical squamous cell carcinoma), DL, HaCat (aneuploid immortal keratinocyte cell line), RAW 264.7 (murine Macrophage), PBMC (peripheral blood mononuclear cell).

Table 2. Microbial sources for synthesis of bionanoparticles and their anticancer activity in various cell lines for the past 5 years.

Microbial species	Microbe type	Nanoparticle type	Size (nm)	Morphology	Anticancer activity (In vitro model)^a	Dose (µg/well)	Exposure time	Major outcome	Reference
Aspergillus deflectus and Penicillium pinophilum	Fungus	Ag/CS	15–40 nm	–	MCF 7, PC3 and A549	12.5–100 μg/mL	24 h	IC50:27.9 and 53μg/mL in MCF 7 and PC3 for AgNPs synthesized from A. deflectus under optimized conditions and no toxicity in A549 No toxicity of AgNPs synthesized from P. pinophilum under optimized conditions in MCF 7 and PC3 and low toxicity in A549	Osman et al. (193)
A. flavus	Fungus	Ag	Average size: 33.5 nm	–	HL-60	5 and 10 μg/mL	6, 12 and 24h	High toxicity at 10 μg/mL after 6 h IC50∼5μg/mL after 12 h. Very high toxicity at 10μg/mL after 12h	Sulaiman et al. (194)
A. flavus SP-3 Trichoderma gamsii SP-4 Talaromyces flavus SP-5 Aspergillus Oryzae SP- 6	Fungus	Ag	20–60 nm	Spherical	HEp2	0–1000 μg/mL	24 h	IC50: 23μg/mL for T. gamsii SP-4, 100 µg/mL for A. flavus SP-3, 39 µg/mL, for T. flavus SP-5, and 36 µg/mL for A. oryzae SP-6	Anand et al. (195)
Aspergillus foetidus	Fungus	Au	30–50 nm	Spherical	A549	10–100µM	12 h	No toxicity	Roy et al. (196)
Bacillus cereus	Bacterium	Cu	11–33 nm	Spherical	HaCat, Vero, hFOB, MCF 7, A549, CaCO2, Neuro-2a, HCT 116, RAW 264.7 and HepG2	20–60 μg/mL	48 h	IC50: ∼20, ≥20, ≥60 μg/mL in hFOB, HaCat and Vero, respectively IC50:3.27 μg/mL in A549; IC50: ≤20 μg/mL in Neuro-2a and RAW 264.7; IC50: ≥20 μg/mL in MCF 7, CaCO2 and HepG2; IC50: ∼40 μg/mL in HCT 116	Tiwari and colleagues (91)
Bacillus cereus	Bacterium	TiO2	69–140 nm	Spherical	HEp2 and Vero cells	0.008–0.5 mg/mL	4 h	IC50: 0.465 mg/mL in HEp2 Low toxicity in Vero	Sunkar et al. (197)
Bacillus cereus (ATCC 14579) and Escherichia fergusonii (ATCC 35469)	Bacterium	Ag	10–20 nm for both of bacteria	Spherical and hexagonal for both of bacteria	NIH3T3 D4	–	24 h	≤0.25 mg/100 µL is nontoxic and 1 mg/100 µL is toxic for AgNPs from B. cereus. ≤ 0.0625 mg/100 µL is nontoxic and 0.25 mg/100 µL is toxic for AgNPs from E. fergusonii	Pourali and Yahyaei (198)
Bacillus flexus	Bacterium	Au	Average size: 20 nm	Different shapes (irregular, spherical, triangular)	MCF-7	25–200 μM/mL	24h	No toxicity	Murugan et al. (199)
Bacillus sp. MSh-1	Bacterium	Se	80–220 nm	Spherical	MCF-7	0–200 μg/mL	24 h	IC50: 41.5 ± 0.9μg/mL	Forootanfar et al. (200)
Bacillus subtilis	Bacterium	Cr(III)	4–50 nm (Average size: 20 nm)	Spherical	HEK 293	0.1–50 µL (1 mM)	48 h	At 50 µL(1 mM) the viability of HEK 293 cells was 83.5 ± 1.66%	Kanakalakshmi et al. (201)
Beauveria bassiana	Fungus	Ag	20.44 – 34.16 nm	Spherical	HeLa	3.125–50 μg/mL	24 h	IC50: 28.8 ± 2.5μg/mL	Prabakaran and colleagues (38)
Cryptococcus laurentii (BNM 0525)	Yeast	Ag	35 ± 10	–	MCF-7, T47D and MCF10-A	0–5 μg/mL	12 h	Significant toxicity above 2.5 μg/mL in MCF-7 and T47D but slight toxicity in MCF10-A	Ortega and colleagues (71)
Endophytic Fungus	Fungus	Au	15–35 nm	Spherical	HEp2 and Vero cells	1.17–75 μg/mL	4 h	IC50: 23 μg/mL in Hep2 IC50: 12 μg/mL in Vero	Nachiyar et al. (202)
Enterococcus sp.	Bacterium	Au	6–13 nm	Spherical	HepG2 and A549	1–100 μg/mL	24 h	IC50: 100μg/mL	Rajeshkumar (203)
Enterococcus sp.	Bacterium	Ag	10 to 80 nm	Spherical	HepG2 and A549	1–100 μg/mL	24 h	IC50: 50μg/mL in HepG2 IC50: 100μg/mL in A549	Rajeshkumar et al. (204)
Fusarium oxysporum	Fungus	Terbium oxide (Tb2O3)	10 nm	Spherical	MG-63, Saos-2 and normal Primary osteoblast	(0.023–0.373 μg/mL	48 h	IC50: 0.102 μg/mL in MG-63 and Saos-2 ≤ 0.373μg/mL low toxicity in normal Primary osteoblast	Iram et al. (205)
Fusarium oxysporum	Fungus	Au	10–40 nm	Spherical	ZR-75-1, Daudi and PBMC	5–500 μg/mL	24 h	Moderate toxicity in ZR-75-1 and Daudi, but no toxicity in PBMC	Ahmad Siddiqui and colleagues (70)
Fusarium oxysporum	Fungus	Ag	5–13 nm	Spherical	MCF-7	0–220 μg/cm^3	–	IC50:121.23 μg/cm^3	Husseiny et al. (206)
Fusarium oxysporum (Fungus)	Fungus	Ag	10–15 nm	Quasi-spherical	C26 and HaCaT	2–16 μg/mL	24 h	No toxicity at ≤6 μg/mL in HaCaT. Significant toxicity at ≥8 μg/mL in C2 6	Potara and colleagues (74)
Halococcus salifodinae BK18	Bacterium	Se	Average size: 28 nm	Rod and hexagonal	HeLa and HaCat	10–150 μg/mL	24 h	IC50∼50 μg/mL in HeLa, No toxicity in HaCat	Srivastava et al. (207)
Humicola sp.	Fungus	Ag	5–25 nm	Spherical	NIH3T3 and MDA-MB-231	50–1000 μg/mL	24 h	Very low toxicity at 250 μg/mL in both cell line Significant toxicity at 1000 μg/mL in both cell line	Syed and colleagues (93)
Humicola spp.	Fungus	Au	18–24 nm	Spherical	NIH3T3 and MDA-MB-231	50–1000 μg/mL	24 h	No toxicity at 50 μg/mL in both cell line Significant toxicity at ≥250 μg/mL in both cell line	Syed et al. (208)
Klebsiella pneumoniae (KACC 11402)	Bacterium	Au	16–36 and 24–50 nm	Spherical	3T3L1, H9c2 and HepG2	0.01–1000 μg/mL	24 and 48 h	No toxicity	Kalpana and colleagues (92)
Moraxella osloensis	Bacterium	Titanium dioxide (TiO2)	60–150 nm	Irregular	HaCaT and HEp2	8–100 μg/mL	–	IC50: 55 μg/mL in HaCaT IC50: 172 μg/mL in HEp2	Valli Nachiyarand colleagues (103)
Nocardiopsis sp.	Marine actinobacterium	Au	Average size: 11.57 ± 1.24 nm	Spherical	HeLa	50–400 μg/mL	24 h	IC50: 300 μg/mL	Manivasagan et al. (209)
Nocardiopsis sp.	marine actinobacterium	Au	10–50 nm Average size: 39 ± 2 nm	Spherical and triangular	HeLa	50–500 μg/mL	24, 48 h	IC50:350 and 250 μg/mL after 24 h and 48 h of incubation	Manivasagan and Oh (210)
Nocardiopsis sp. MBRC-1	Bacterium	Ag	Average size: 45 ± 0.15 nm	Spherical	HeLa	50–250 μg/mL	24 h	IC50: 200 μg/mL	Manivasagan et al. (211)
Nocardiopsis valliformis OT1 strain	Alkaliphilic actinobacterium	Ag	5–50 nm	Spherical	HeLa	25–100 μg/mL	48 h	IC50: 100μg/mL	Rathod et al. (212)
Penicillium brevicompactum	Fungus	Au	10–120 nm	Spherical, triangular and hexagonal	C2C12	200–2000ng/mL	24, 48, 72 h	IC50: >1000 ng/mL after 24h IC50: >200 ng/mL after 48h Significant toxicity after 72 h at any range of concentration	Mishra and colleagues (94)
Penicillium decumbens (MTCC-2494)	Fungus	Ag	30–60 nm	Spherical	A-549 and Vero cells	20–120 μg/mL	24 and 48 h	A-549 IC50:80 and 60 μg/mL after 24 h and 48 h of incubation, respectively. Vero cell IC50: 100μg/mL after 24 h of incubation	Majeed and colleagues (100)
Pleurotus djamor var. roseus	Fungus	Ag	5–50 nm	Spherical	PC3	1–6 μg/mL	24 h	IC50: 10 μg/mL	Raman et al. (213)
Pleurotus ostreatus	Fungus	Ag	4–15 nm	Spherical	MCF-7	10–640 μg/mL	24 h	IC50∼160 μg/mL	Yehia and Al-Sheikh (214)
Pseudomonas aeruginosa (JQ989348)	Bacterium	Ag	13–76 nm	Spherical	Human carcinoma cervical cell line	5–100 μg/mL	24 h	100% toxicity at 40μg/mL	Ramalingam et al. (215)
Schizophyllum commune	Fungus	Ag	51–93 nm	Spherical	HEP -2	10–100 μg/mL	24 h	IC50:53 μg/mL	Arun et al. (216)
Stenotrophomonas maltophilia	Bacterium	Ag	Average size: ∼93 nm	Cuboidal	HeLa and Splenocyte cells	0–500 μg/mL	48 h	IC50: >31.25 μg/mL in HeLa IC50: >250 μg/mL in Splenocyte cells	Oves et al. (217)
Streptomyces naganishii (MA7)	Actinobacteria	Ag	5–50 nm	Spherical	HeLa	0.1–300 μg/mL	48 h	IC50: 1.53 μg/mL LD50:24.39 μg/mL	Shanmugasundaram et al. (218)
Streptomyces rochei MHM13	Actinomycetes	Ag	22–85 nm	Spherical	HepG2, HCT-116, MCF-7, PC-3, A-549, CACO, HEp-2 and HeLa	1.56–50 µg/well	24 h	IC50:32.90 µg/Well in HepG2 IC50:9.05 µg/Well in HCT-116 IC50:40.00 µg/Well in MCF-7 IC50: 48.50 µg/Well in PC-3 IC50: 42.10 µg/Well in A-549 IC50: >50 µg/Well in CACO IC50: >50 µg/Well in HEp-2 IC50: >50 µg/Well in HeLa	Abd-Elnaby et al. (219)
Trichoderma koningii	Fungus	Au	10–14 nm	Spherical	LoVo and LoVo/DX	1–1000 μg/mL	24 h	IC50:33.04 ± 4.9 μg/mL in LoVo IC50:28.88 ± 2.9 μg/mL in LoVo/DX	Maliszewska (75)
Trichoderma viride	Fungus	Ag	5–40 nm	–	MCF-7	1–100 µg/mL	24 h	Low toxicity ≤10 µg/mL, but toxicity gradually increased over 10 µg/mL	Kulandaivelu and Gothandam (220)
Xylorious	Fungus	Ag	–	Spherical	HT-29	7.8–1000 μg/mL	48 h	IC50:62.5 μg/mL	Varsha B (48)

^aCancer and normal Cell Lines: HeLa (human cervical cancer), A549 (human lung adenocarcinoma), HepG2 (hepatic cancer), MDA-MB-231 and MCF-7 (human breast adenocarcinoma), PC-3 (human prostate carcinoma), MG-63 (osteosarcoma cell), HT-29 (human colorectal adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), HL-60 (human acute myeloid leukemia), HEp-2 (human larynx carcinoma), ZR-75-1 (human caucasian breast carcinoma), DAUDI (human burkitt’s lymphoma), T47D (human breast cancer), LoVo (human colon adenocarcinoma), LoVo/DX (multidrug resistance human colon adenocarcinoma sub-line), HaCat (aneuploid immortal keratinocyte cell line), hFOB (homo sapiens bone), Neuro-2a (mus musculus brain neuroblastoma), HCT 116 (homo sapiens colon colorectal carcin), RAW 264.7 (murine Macrophage), NIH3T3 (mouse fibroblast), Saos-2 (homo sapiens bone osteosarcoma), PBMC (peripheral blood mononuclear cell).

Figure 4. Recent advances in proposed mechanisms for anticancer activity shown by colloidal biogenic silver nanoparticles (AgNPs) (Adapted with permission from Ovais et al. (21)).

Figure 5. Fluorescence images of HeLa cancer cells which were incubated in the absence of Au/Ce NCs (A), in the presence of 50 μmol/L (B) and 150 μmol/L (C) Au/Ce NCs solutions for 24 h. (D) The fluorescence intensity variations along cross-sections a (in A), b (in B) or c (in C). Fluorescence images were collected by applying fluorescence excitation wavelength at 488 nm (Adapted with permission from Ge et al. (118)).

Figure 6. Tumor nude mice models of cervical carcinoma in vivo imaging. (A) In vivo fluorescence imaging 24 h after a subcutaneous injection of 5 mmol/L Au/Ce NCs solution near the tumor. (B) In vivo fluorescence imaging 24 h after an intravenous injection of 5 mmol/L Au/Ce NCs solution through the tail. (C) Control nude mice without tumor after intravenous injection equivalent to PBS through the tail. Fluorescent Au/Ce NCs were observed inside the tumors using a 455 nm excitation wavelength (Adapted with permission from Ge et al. (118)).

Figure 7. Biosynthesis of AuNPs by employing heavy metal binding proteins (HMBPs) in recombinant E. coli and subsequent conjugation of doxorubicin. Doxorubicin-loaded AuNPs complexes can be easily fragmented to release doxorubicin from AuNPs to defuse through the cancer cell (Adapted with permission from Seo et al. (124)).

Figure 8. Major challenges for scientists before biosynthesized nanomaterials enter clinical trials for cancer theranostics.

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