The recent development of topical nanoparticles for annihilating skin cancer

Figures & data

Figure 1. Structure of Skin membrane barrier showing different layers of skin tissue like stratum corneum followed by epidermis and lastly dermis along with different routes of permeation through skin.

Figure 2. Classification of Skin cancer.

Figure 3. Different types of Nanocarriers used in topical/dermal therapy.

Table 1. Different types of research studies showing performance of different nanoparticle system in skin cancer treatment with major emphasis given to 5-fluorouracil with some studies with different API.

Authors	API	Nano-particle system	Size & Zeta Potential	Routes of administration	Results	Ref.
Haase, A., et al.	5-FU	Gold Nanoparticles	16.02nm Zp: + 47.81 mV	Topical	An 18-fold reduction in the tumour was observed when compared to untreated or free 5-FU gel.	(Safwat et al. 2016)
Ishioka, P., et al.	5-FU	Dendrimers		Topical	The pre-treatment of dendrimers in a solvent such as isopropyl myristate (IPM) resulted in an alteration of the skin barrier, which in turn increased the diffusion of 5-FU into the skin tissue..	(Venuganti and Perumal 2009)
Al-Harbi, K.S	5-FU	Chitin Nanogel	125-140nm Zp: + 31.9 mV	Topical	The positive zeta potential of chitin NP aided in the development of a strong interaction with the Stratum corneum, which ultimately resulted in the loosening of keratin and the accumulation of drugs in the skin's deeper layers.	(Ahmad et al. 2020)
Zheng, L., et al.	5-FU	Pheroid™ Droplets	251nm Zp: - −28.95 ± 2.45 mV	Topical	Pheroid^TM vesicles fluidize the stratum corneum and reduce its barrier properties, allowing the drug to be transported into the skin more effectively.	(Torin Huzil et al. 2011)
Yassin, A.E.B., et al	5-FU- Orange juice extract.	Nanoparticles	25nm Zp: −39 ± 2.10 mV	Topical	It was discovered that when these nanoparticles were combined with a cream base, the survival rate of mice was increased by as much as 68% or more.	(Mohammad et al. 2019)
Safwat, M.A., et al.	5-FU	Nanoemulsion	100nm Zp: −15 mV	Topical	PEG 400, which acts as a co-surfactant, interacted with the stratum corneum and altered the barrier properties, resulting in increased skin permeation. The composition contained an oil – Capyrol (propylene glycol monocaprylate), a skin permeation enhancer – Transcutol (purified diethylene glycol monoethyl ether), and acted as a surfactant.	(Siddalingam and Chidambaram 2016)
Mahira, S., et al.	Diindolylmethane derivative (DIM-D)	Deformable ultra-flexible nanovesicles	110.5nm Zp: +16.02 mV	Topical	The positively charged vesicles interacted with the negatively charged lipid lamellae of the stratum corneum, resulting in an increase in the amount of antioxidant derivative deposited on the skin's surface. Consequently, it may be able to prevent the return of UV-induced skin cancer in mice.	(Bagde et al. 2018)
Gupta, M et al.	1-(−1-naphthyl) piperazine (1-NPZ)	Lipid vesicles	212nm Zp: 3.3 mV	Topical	This system contained DMSO, which served as a skin penetration enhancer, and the nanovesicle system prevented UV-B-induced skin cancer while also inducing tumour cell death through oxidative stress in the test subjects.	(Menezes et al. 2016)
Gao, C., et al.	SiRNA	Mesoporous silica nanoparticles	250 50 nm Zp: +30 mV	Topical	It was discovered that mesoporous silica nanoparticles enhanced the deposition of quercetin within the epidermis, and quercetin is an antioxidant and anti-cancer agent, and it has the potential to be used as a skin cancer preventive measure in the future.	(X. Li et al. 2011)
Mahant, S., et al.	Plasmid DNA	Gold Nanoparticles	19.9 ± 7.7 nm Zp: 16.81 mV	Topical	There are gold nanoparticles in this system, and they have been functionalized with the HIV-1 twinarginine translocation peptide. As a result, the penetration of the drug across the stratum corneum was improved, and the treatment of cutaneous melanoma was found to be effective.	(Niu et al. 2017)
	UV filters like Avobenzone and Octorylene	Self-assembled nanoparticles	216 nm Zp: −53 mV	Topical	The nanoparticles composed of PLA-HPG block co-polymer are intended to increase the retention time on the skin while also preventing skin damage caused by ultraviolet light exposure.	(V. Krishnan and Mitragotri 2020)
Kim, B., et al.	Apigenin (Ap)	PLGA Nanoparticles	101.3 nm Zp: −12.1 mV	Topical + Oral	These nanoparticles outperformed free drug in terms of efficacy and tissue damage when it came to preventing skin cancer, according to the results of the study.	(Sreemanti Das et al. 2013)
Ambekar, R.S	Radioactive Holmium 166 (166 Ho)	Electrospun polyacrylonitrile (PAN) Nanofibres	174-208 nm Nanofibres 52 nm NPs	Localised Radiation	PAN nanofibres were conjugated with non-radioactive 165 Ho nanoparticles to create a non-radioactive composite. It was decided to make radiotherapeutic bandages. In this system, 165 Ho non-radioactive NPs are converted to radioactive 166 Ho, which has a significant impact on the reduction of cSCC tumours in mice.	(Munaweera et al. 2014)

Figure 4. Various nanocarriers of different classes – 2a- Lipid based nanocarriers (Liposome), 2b- Polymer based nanocarriers (Polymeric micelle) 2c- Inorganic nanocarriers (Gold nanoparticle)-1479 with permission from Springer Nature - License no: 5010250744068).

Figure 5. TEM images showing the uniform size of 20 nm of Silica NPs (Adapted from Lee et al. 2016. A quantitative study of nanoparticle skin penetration with interactive segmentation. Medical & biological engineering & computing, 54(10), pp.1469-1479 with permission from Springer Nature – License no: 5010250744068).

Figure 6. Negative charge image (Adapted from Lee et al. 2016. A quantitative study of nanoparticle skin penetration with interactive segmentation. Medical & biological engineering & computing, 54(10), pp.1469-1479 with permission from Springer Nature - License no: 5010250744068)

Figure 7. Positive charge image (Adapted from Lee et al. 2016. A quantitative study of nanoparticle skin penetration with interactive segmentation. Medical & biological engineering & computing, 54(10), pp.1469-1479 with permission from Springer Nature - License no: 5010250744068)

Figure 8. 7 Quantification results for each group. (A) Mean, (B) integrated density, (C) skewness, (D) kurtosis, (E) area fraction, (F) penetration depth. *vs. Day 0 Group, ^†vs. Day 2 Group, ^‡vs. Day 4 Group (Student's t test, P < 0.05).

Safwat MA, Soliman GM, Sayed D, Attia MA. 2016. Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal cancer cells. Int J Pharm. 513(1-2):648–658.

 PubMedGoogle Scholar

Venuganti VVK, Perumal OP. 2009. Poly (amidoamine) dendrimers as skin penetration enhancers: influence of charge, generation, and concentration. J Pharm Sci. 98(7):2345–2356.

 PubMed Web of Science ®Google Scholar

Ahmad A, Mubharak N, Naseem K, Tabassum H, Rizwan M, Najda A, … Shaheen A. 2020. Recent advancement and development of chitin and chitosan-based nanocomposite for drug delivery: critical approach to clinical research. arab. J. Chem. 13:8935–8964.

 Web of Science ®Google Scholar

Torin Huzil J, Sivaloganathan S, Kohandel M, Foldvari M. 2011. Drug delivery through the skin: molecular simulations of barrier lipids to design more effective noninvasive dermal and transdermal delivery systems for small molecules, biologics, and cosmetics. Wiley Interdiscip Rev: Nanomed Nanobiotechnol. 3(5):449–462.

 PubMed Web of Science ®Google Scholar

Mohammad O, Faisal SM, Ahmad N, Rauf MA, Umar MS, Mujeeb AA, … Ajmal M. 2019. Bio-mediated synthesis of 5-FU based nanoparticles employing orange fruit juice: a novel drug delivery system to treat skin fibrosarcoma in model animals. Sci Rep. 9(1):1–14.

 PubMedGoogle Scholar

Siddalingam R, Chidambaram K. 2016. Topical nano-delivery of 5-fluorouracil: preparation and characterization of water-in-oil nanoemulsion. Tropical Journal of Pharmaceutical Research. 15(11):2311–2319.

 Web of Science ®Google Scholar

Bagde A, Mondal A, Singh M. 2018. Drug delivery strategies for chemoprevention of UVB-induced skin cancer: A review. Photodermatol Photoimmunol Photomed. 34(1):60–68.

 PubMed Web of Science ®Google Scholar

Menezes AC, Campos PM, Euletério C, Simões S, Praça FSG, Bentley MVLB, Ascenso A. 2016. Development and characterization of novel 1-(1-naphthyl) piperazine-loaded lipid vesicles for prevention of UV-induced skin inflammation. Eur J Pharm Biopharm. 104:101–109.

 PubMed Web of Science ®Google Scholar

Li X, Xie QR, Zhang J, Xia W, Gu H. 2011. The packaging of siRNA within the mesoporous structure of silica nanoparticles. Biomaterials. 32(35):9546–9556.

 PubMed Web of Science ®Google Scholar

Niu J, Chu Y, Huang Y-F, Chong Y-S, Jiang Z-H, Mao Z-W, … Gao J-Q. 2017. Transdermal gene delivery by functional peptide-conjugated cationic gold nanoparticle reverses the progression and metastasis of cutaneous melanoma. ACS Appl Mater Interfaces. 9(11):9388–9401.

 PubMed Web of Science ®Google Scholar

Krishnan V, Mitragotri S. 2020. Nanoparticles for topical drug delivery: potential for skin cancer. Adv Drug Delivery Rev. 153:87–108. doi:10.1016/j.addr.2020.05.011.

 PubMed Web of Science ®Google Scholar

Das S, Das J, Samadder A, Paul A, Khuda-Bukhsh AR. 2013. Efficacy of PLGA-loaded apigenin nanoparticles in benzo [a] pyrene and ultraviolet-B induced skin cancer of mice: mitochondria mediated apoptotic signalling cascades. Food Chem Toxicol. 62:670–680.

 PubMed Web of Science ®Google Scholar

Munaweera I, Levesque-Bishop D, Shi Y, Di Pasqua AJ, Balkus Jr KJ. 2014. Radiotherapeutic bandage based on electrospun polyacrylonitrile containing holmium-166 iron garnet nanoparticles for the treatment of skin cancer. ACS Appl Mater Interfaces. 6(24):22250–22256.

 PubMed Web of Science ®Google Scholar

Lee O, Lee SH, Jeong SH, Kim J, Ryu HJ, Oh C, Son SW. 2016. A quantitative study of nanoparticle skin penetration with interactive segmentation. Med Biol Eng Comput. 54(10):1469–1479.

 PubMed Web of Science ®Google Scholar

Data availability statement

Data sharing is not applicable to this article as no new data were created or analysed in this study.