Combination cancer imaging and phototherapy mediated by membrane-wrapped nanoparticles

Figures & data

Scheme 1. Overview of theranostic NPs for dual cancer imaging and PTT. (A) Depiction of the process to use NPs for real-time imaging to guide PTT. (B) Summary of various NP formulations that have used pre-clinically as phototheranostics. Red spheres in the polymer, lipid and silica formulations indicate encapsulated light-responsive dyes. Created with BioRender.com.

Scheme 2. Cell-derived membranes include distinct molecules that facilitate immune evasion, enable binding to non-homotypic cells or promote binding to homotypic cells. Together, these features enhance the tumor accumulation of MWNPs. Created with BioRender.com.

Table 1. List of common abbreviations found throughout this review.

Abbreviation	Expanded term	Abbreviation	Expanded term
AF	Activated fibroblast	MPS	Mononuclear phagocytic system
BBB	Blood–brain barrier	MRI	Magnetic resonance imaging
BTB	Blood–tumor barrier	MSC	Mesenchymal stem cell
CT	Computed tomography	MWNP(s)	Membrane-wrapped nanoparticle(s)
CW	Continuous wave	NIR	Near-infrared
DOX	Doxorubicin	NP(s)	Nanoparticle(s)
DTX	Docetaxel	PA	Photoacoustic
Ex	Excitation	PDT	Photodynamic therapy
Em	Emission	PEG	Poly(ethylene glycol)
FA	Folic acid	PLGA	Poly(lactic-co-glycolic acid)
FL	Fluorescence	PTT	Photothermal therapy
HSP	Heat shock protein	RBC	Red blood cell
HU	Hounsfield unit	SERS	Surface-enhanced Raman scattering
ICG	Indocyanine green	siRNA	Small interfering ribonucleic acid
IV	Intravenous	SNR	Signal-to-noise ratio
Luc	Luciferase	SPN(s)	Semiconducting polymer nanoparticle(s)
MDSC	Myeloid-derived suppressor cell	TPP	Triphenylphosphine
MNC	Magnetic nanocluster

Other abbreviations such as those for specific MWNP formulations are defined where called out in the text.

Table 2. Comparison of different imaging modalities that have been utilized in combination with phototheranostic NPs.

Imaging modality	Excitation source	Tissue penetration depth	Resolution	Pros	Cons
PA imaging	Light	10 mm–9 cm	30–700 µm	High resolution High tissue penetration Fast acquisition	Small imaging surface area
MRI	Magnetic field	>10 cm	50 µm–2 mm	High resolution Large imaging surface area	Low sensitivity Slow acquisition
FL imaging	Light	1–20 mm	1–500 µm	High resolution Fast acquisition	Low tissue penetration
CT	X-ray	>10 cm	50 µm–1 mm	High resolution High relative speed	Radiation exposure
SERS imaging	Light	5–25 mm	<1 µm	High sensitivity High photostability	Limited tissue penetration Low relative speed

Figure 1. Representative MWNP used for PTT, PA imaging and FL imaging. (A) Scheme of ICNP. (B) FL and PA images of MCF-7 breast cancer tumors in mice following IV injection with either ICG, INPs or ICNPs. (C) Thermal images of MCF-7 tumor-bearing mice exposed to an 808 nm laser for 5 min (1 W/cm²) after IV injection of PBS, ICG, INPs or ICNPs. (D) Tumor growth curves of different groups after treatments (n = 5). Reprinted (adapted) with permission from Chen et al. [8,p.10049]. Copyright 2016 American Chemical Society.

Figure 2. Representative example of membrane-wrapped semiconducting material for combined PTT and PA imaging. (A) Hybrid membrane-coated DOX-loaded hollow cupper sulfide NPs (DCuS@[RBC–B16] NPs) were explored for combination imaging/PTT/chemotherapy of melanoma. (B) CuS@[RBC–B16] NPs achieved a strong localized PA signal in tumors 4 h post IV injection. (C) Blood retention time of CuS NPs that were unwrapped or coated with RBC membranes, B16-F10 membranes or hybrid RBC–B16 membranes. (D) Biodistribution of unwrapped, RBC-wrapped, B16-wrapped or hybrid membrane-wrapped CuS NPs in tumor-bearing mice after IV injection. (E) Relative tumor volume of mice exposed to different treatments (1: NS, 2: CuS@[RBC–B16], 3: DOX, 4: NIR laser (1064 nm, 1 W/cm²), 5: DCuS@[RBC–B16], 6: CuS@[RBC–B16] with NIR laser, 7: DCuS@[RBC–B16] with NIR laser). Reprinted (adapted) with permission from Wang et al. [25,p.5241]. Copyright 2018 American Chemical Society.

Figure 3. Example of a MWNP used for dual FL imaging and PTT. (A) NIR-II FL images of mice bearing glioblastoma tumors following IV injection with either IR792, DINPs (unwrapped NPs loaded with IR792) or MDINPs (macrophage membrane-wrapped NPs loaded with IR792). (B) Representative bioluminescence images of tumors after treatment with different agents combined with 808 nm irradiation. (C) Survival rates of mice in different groups after PTT (n = 5). Reprinted (adapted) with permission from Lai et al. [13,p.48]. Copyright 2019 American Chemical Society.

Table 3. Summary of studies that have developed MWNPs for image-guided PTT.

NP components	Membrane source(s)	Laser parameters for in vivo PTT	Imaging mode(s)	Tumor model	Citation
PLGA loaded with ICG	MCF-7 breast cancer modified with PEG	808 nm 1 W/cm^2 5 min	FL, PA	MCF-7 breast cancer	Chen et al. [8,p.10049]
PEG-modified tungsten disulfide nanosheets loaded with DOX and ICG	RBC modified with FA	808 nm 1 W/cm^2 5 min	PA	HeLa cervical cancer	Long et al. [9,p.5088]
Poly(caprolactone) (PCL)–PEG–PCL triblock copolymer loaded with IR780 and DTX	RBC	808 nm 1.5 /cm^2 5 min	FL, PA	MCF-7 breast cancer	Yang et al. [12,p.3208]
Semiconducting PCPDTBT	Activated fibroblast	808 nm 0.3 W/cm^2 5 min	FL, PA	4T1 breast cancer	Li et al. [15,p.8520]
Narrow bandgap electron donor–acceptor semiconducting polymer Acceptor segment: thiophene‑fused benzodifurandione‑based oligo(p‑phenylene vinylene) Donor segment: thieno[3,2‑b]thiophen‑2‑yl) benzo[1,2‑b:4,5‑b′]dithiophene	RBC	808 nm 0.5 W/cm^2 10 min	PA	4T1 breast cancer	Zheng et al. [16]
Hollow copper sulfide loaded with DOX	Hybrid: B16-F10 melanoma and RBC	1064 nm 1 W/cm^2 5 min	PA	B16-F10 melanoma	Wang et al. [25,p.5241]
Melanin	RBC	808 nm 2 W/cm^2, 5 min or 1 W/cm^2, 10 min	PA	A549 lung cancer	Jiang et al. [23,p.29]
Melanin	Hybrid: MCF-7 breast cancer and RBC	808 nm 1 W/cm^2 10 min	PA	MCF-7 breast cancer	Jiang et al. [24,p.292]
Prussian blue NPs modified with zinc glutamate and with TPP conjugated lonidamine	HepG2 liver cancer	808 nm 1 W/cm^2 5 min	PA	HepG2 liver cancer	Wang et al. [26,p.37563]
Gold nanostars	RBC	785 nm 2 W/cm^2 5 min	PA	HepG2 liver cancer	Huang et al. [17]
Liposome loaded with IR1048	Platelet	1064 nm 1 W/cm^2 5 min	PA	C6 glioma	Geng et al. [14,p.55624]
Fe3O4	RBC	808 nm 5 W/cm^2 5 min	MRI	MCF-7 breast cancer	Ren et al. [22,p.13]
Fe3O4	RBC	808 nm 5 W/cm^2 5 min	MRI	MCF-7 breast cancer	Rao et al. [20,p.3496]
Fe3O4	MDSC	808 nm 5 W/cm^2 5 min	MRI	B16-F10 melanoma	Yu et al. [19]
Fe3O4@Cu2-xS	RBC	1064 nm 0.8 W/cm^2 10 min	MRI	HeLa cervical cancer	Lin et al. [21,p.1202]
Fe3O4 coated with polydopamine and siRNA	MSC	808 nm 0.6 W/cm^2 6 min	MRI	DU145 prostate cancer	Mu et al. [51,p.3895]
PLGA loaded with ICG and PFCE	A549 lung cancer	765 nm 400 mW/cm^2 15 min	PA, MRI, FL	A549 lung cancer	Li et al. [47,p.57290]
PCL and pluronic copolymer F68 NP loaded with ICG	B16-F10 melanoma, 4T1 breast cancer or COS7 fibroblast	808 nm 1 W/cm^2 5 min	FL	U87 glioblastoma	Wang et al. [10]
Liposomes loaded with ICG	C6 glioma	808 nm 1 W/cm^2 5 min	FL	C6 glioma	Jia et al. [11,p.386]
DSPE-PEG NPs loaded with IR792	Macrophages	808 nm 0.8 W/cm^2 5 min	FL	U87 glioblastoma	Lai et al. [13,p.48]
Hollow Bi2Se3 loaded with QE	Macrophage	808 nm 2 W/cm^2 5 min	FL, CT	4T1 breast cancer	Zhao et al. [28,p.31124]
AuNDs loaded with ICG and functionalized with TPP	Macrophage	1064 nm, 1 W/cm^2, 10 min and/or 808 nm, 0.3 W/cm^2, 5 min	FL, PA, SERS imaging	MDA-MB-231 breast cancer	Sun et al. [18,p.10778]
Black-titanium (TiO2) NPs functionalized with iridium complexes	HeLa cervical cancer	1064 nm 1 W/cm^2 10 min	PA, two-photon imaging	HeLa cervical cancer	Shen et al. [29,p.120979]
ZGGO coated with mesoporous silica and loaded with IR825 and Ir	Hybrid: CT26 colorectal cancer and RAW 264.7 macrophage	808 nm 1 W/cm^2 5 min	Long persistent luminescence imaging	CT26 colorectal cancer	Wang et al. [27,p.7105]

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Data availability statement

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