Light-responsive Nanocarriers Research Articles

Optically Controlled CRISPR-Cas9 and Cre Recombinase for Spatiotemporal Gene Editing: A Review.

CRISPR-Cas9 and Cre recombinase, two tools extensively used for genome interrogation, have catalyzed key breakthroughs in our understanding of complex biological processes and diseases. However, the immense complexity of biological systems and off-target effects hinder clinical applications, necessitating the development of platforms to control gene editing over spatial and temporal dimensions. Among the strategies developed for inducible control, light is particularly attractive as it is noninvasive and affords high spatiotemporal resolution. The principles for optical control of Cas9 and Cre recombinase are broadly similar and involve photocaged enzymes and small molecules, engineered split- and single-chain constructs, light-induced expression, and delivery by light-responsive nanocarriers. Few systems enable spatiotemporal control with a high dynamic range without loss of wild-type editing efficiencies. Such systems posit the promise of light-activatable systems in the clinic. While the prospect of clinical applications is palpably exciting, optimization and extensive preclinical validation are warranted. Judicious integration of optically activated CRISPR and Cre, tailored for the desired application, may help to bridge the "bench-to-bedside" gap in therapeutic gene editing.

Copper indium selenium nanomaterials for photo-amplified immunotherapy through simultaneously enhancing cytotoxic T lymphocyte recruitment and M1 polarization of macrophages.

Photoactivated immunotherapy has promising therapeutic efficacy for treating malignancies, especially metastatic tumors. In this study, an erythrocyte membrane-encapsulated copper indium selenium (RCIS) semiconductor nanomaterial was developed to eliminate primary and metastatic tumors, in which copper ions can induce chemodynamic performance, and the narrow band gap endows RCIS with the properties of near-infrared (NIR) light-activated photothermal and photodynamic amplified immunotherapy. Furthermore, RCIS can be used as a nanocarrier to form RNCIS nanoparticles (NPs) by loading NLG919, which blocks the indoleamine 2,3-dioxygenase-1. Under NIR light irradiation, RNCIS NPs release NLG919 at tumor sites via photothermal properties, thereby promoting the recruitment of cytotoxic T lymphocytes and M1 polarization of macrophages, targeting the activation and amplification of immune responses. Herein, in vitro and in vivo studies showed that RNCIS NPs effectively kill cancer cells and eliminate primary and metastatic tumors. Therefore, this study suggests that semiconductor nanomaterials with narrow bandgaps have great potential as photoimmunotherapy agents and NIR light-responsive nanocarriers for controlled release, providing a great paradigm for synergetic tumor photoimmunotherapy. STATEMENT OF SIGNIFICANCE: The Erythrocyte membrane-coated, NLG919-loaded copper indium selenium (RNCIS) semiconductor was designed for eliminating primary and metastatic tumors. RNCIS exhibits chemodynamic, photodynamic, and photothermal activated immunotherapy by inhibiting indoleamine 2,3-dioxygenase-1. This can enhance the recruitment of cytotoxic T lymphocyte and M1 polarization of macrophage, leading to higher synergetic photo-immune therapeutic efficacy.

Spatiotemporally controlled drug delivery via photothermally driven conformational change of self-integrated plasmonic hybrid nanogels

BackgroundSpatiotemporal regulation is one of the major considerations for developing a controlled and targeted drug delivery system to treat diseases efficiently. Light-responsive plasmonic nanostructures take advantage due to their tunable optical and photothermal properties by changing size, shape, and spatial arrangement.ResultsIn this study, self-integrated plasmonic hybrid nanogels (PHNs) are developed for spatiotemporally controllable drug delivery through light-driven conformational change and photothermally-boosted endosomal escape. PHNs are easily synthesized through the simultaneous integration of gold nanoparticles (GNPs), thermo-responsive poly (N-isopropyl acrylamide), and linker molecules during polymerization. Wave-optic simulations reveal that the size of the PHNs and the density of the integrated GNPs are crucial factors in modulating photothermal conversion. Several linkers with varying molecular weights are inserted for the optimal PHNs, and the alginate-linked PHN (A-PHN) achieves more than twofold enhanced heat conversion compared with others. Since light-mediated conformational changes occur transiently, drug delivery is achieved in a spatiotemporally controlled manner. Furthermore, light-induced heat generation from cellular internalized A-PHNs enables pinpoint cytosolic delivery through the endosomal rupture. Finally, the deeper penetration for the enhanced delivery efficiency by A-PHNs is validated using multicellular spheroid.ConclusionThis study offers a strategy for synthesizing light-responsive nanocarriers and an in-depth understanding of light-modulated site-specific drug delivery.Graphical

(Nano)platforms in bladder cancer therapy: Challenges and opportunities.

Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo-loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH-, redox-, and light-responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review.

Photo-Induced Drug Release from Polymeric Micelles and Liposomes: Phototriggering Mechanisms in Drug Delivery Systems.

Chemotherapeutic drugs are highly effective in treating cancer. However, the side effects associated with this treatment lower the quality of life of cancer patients. Smart nanocarriers are able to encapsulate these drugs to deliver them to tumors while reducing their contact with the healthy cells and the subsequent side effects. Upon reaching their target, the release of the encapsulated drugs should be carefully controlled to achieve therapeutic levels at the required time. Light is one of the promising triggering mechanisms used as external stimuli to trigger drug release from the light-responsive nanocarriers. Photo-induced drug release can be achieved at a wide range of wavelengths: UV, visible, and NIR depending on many factors. In this review, photo-induced release mechanisms were summarized, focusing on liposomes and micelles. In general, light-triggering mechanisms are based on one of the following: changing the hydrophobicity of a nanocarrier constituent(s) to make it more soluble, introducing local defects within a nanocarrier (by conformational transformation or photo-cleavage of its lipids/polymers chains) to make it more porous or concentrating heat for thermo-sensitive nanocarriers to release their payload. Several research studies were also presented to explore the potentials and limitations of this promising drug release triggering mechanism.

Green Light‐Triggered Intraocular Drug Release for Intravenous Chemotherapy of Retinoblastoma (Adv. Sci. 20/2021)

Light-Triggered Drug Release In article number 2101754, Changyou Zhan, Weiping Wang, and co-workers develop an “intravenous injection plus light-triggered intraocular drug release” strategy to achieve drug accumulation in retinoblastoma. The strategy is demonstrated with a green light-responsive nanocarrier self-assembled by photocleavable trigonal molecules. After intravenous injection of drug-loaded nanocarriers, green light triggers the disassembly of nanocarriers in the retinal blood vessels, which leads to intraocular drug release and accumulation to suppress retinoblastoma growth.

Advances in Functionalized Photosensitive Polymeric Nanocarriers.

The synthesis of light-responsive nanocarriers (LRNs) with a variety of surface functional groups and/or ligands has been intensively explored for space-temporal controlled cargo release. LRNs have been designed on demand for photodynamic-, photothermal-, chemo-, and radiotherapy, protected delivery of bioactive molecules, such as smart drug delivery systems and for theranostic duties. LRNs trigger the release of cargo by a light stimulus. The idea of modifying LRNs with different moieties and ligands search for site-specific cargo delivery imparting stealth effects and/or eliciting specific cellular interactions to improve the nanosystems’ safety and efficacy. This work reviews photoresponsive polymeric nanocarriers and photo-stimulation mechanisms, surface chemistry to link ligands and characterization of the resultant nanosystems. It summarizes the interesting biomedical applications of functionalized photo-controlled nanocarriers, highlighting the current challenges and opportunities of such high-performance photo-triggered delivery systems.

Self-assembled micelle responsive to quick NIR light irradiation for fast drug release and highly efficient cancer therapy

Upconversion nanoparticles (UCNPs) have been used for designing near infrared (NIR) light-responsive nanocarriers and controllable drug release. However, the need for long-term NIR light irradiation over hours impaired their application efficiency. Here we develop a self-assembled micelle of amphipathic polymer P-DASA which degrades via quick NIR light irradiation. UCNPs and DOX are also encapsulated in the micelle for quick drug release. P-DASA is composed of hydrophilic polyethylene glycol segment and photo-responsive hydrophobic donor–acceptor Stenhouse adduct (DASA). Only 5-min NIR irradiation causes the hydrophilicity conversion of P-DASA and the complete disruption of micelle with DOX fast release of 83.7% in 30 min to achieve highly efficient therapy. Moreover, the P-glycoprotein mediated DOX efflux is also diminished by concomitantly producing NO intracellularly. This micelle demonstrates impressive in vivo therapeutic effect, and thus provides an avenue for highly efficient cancer therapy.

The simultaneous role of porphyrins\u2019 H- and J- aggregates and host\u2013guest chemistry on the fabrication of reversible Dextran-PMMA polymersome

Aggregation-induced quenching of porphyrin molecules as photosensitizer significantly reduces the quantum yield of the singlet oxygen generation, and it is able to decrease the efficacy of photodynamic therapy. We utilized amphiphilic copolymers in this work to precisely control porphyrin H-type and J-type aggregations in water. The amphiphilic copolymer bearing azobenzene, β-cyclodextrin, and porphyrin was successfully synthesized by the atom transfer radical polymerization technique. The azobenzene and β-cyclodextrin complex, as a host–guest supramolecular interaction, has great potential in the design of light-responsive nanocarriers. The amphiphilic block copolymer can be self-assembled into polymersomes, whose application in the generation of singlet oxygen has been also tested. We further demonstrate that, due to the stable H- and J-aggregates of porphyrin, which act as noncovalent cross-linking points, the structure of polymersomes can be reversible under light-stimulus. This formation method has the advantage of allowing for both the encapsulation of hydrophilic and hydrophobic molecules and release upon external light without any distinguishable changes in the structure. Furthermore, the morphology and particle size distribution of the polymersomes were also investigated by using transition electron microscopy, dynamic light scattering, and field emission scanning electron microscopy.

Coumarin-Containing Light-Responsive Carboxymethyl Chitosan Micelles as Nanocarriers for Controlled Release of Pesticide.

Currently, controlled release formulations (CRFs) of pesticides in response to biotic and/or abiotic stimuli have shown great potential for providing “on-demand” smart release of loaded active ingredients. In this study, amphiphilic biopolymers were prepared by introducing hydrophobic (7-diethylaminocoumarin-4-yl)methyl succinate (DEACMS) onto the main chain of hydrophilic carboxymethylchitosan (CMCS) via the formation of amide bonds which were able to self-assemble into spherical micelles in aqueous media and were utilized as light-responsive nanocarriers for the controlled release of pesticides. FTIR and NMR characterizations confirmed the successful synthesis of the CMCS-DEACMS conjugate. The critical micelle concentration (CMC) decreased with the increase in the substitution of DEACMS on CMCS, which ranged from 0.013 to 0.042 mg/mL. Upon irradiation under simulated sunlight, the hydrodynamic diameter, morphology, photophysical properties and photolysis were researched by means of dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-vis absorption spectroscopy and fluorescence spectroscopy. Moreover, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model pesticide and encapsulated into the CMCS-DEACMS micelles. In these micelle formulations, the release of 2,4-D was promoted upon simulated sunlight irradiation, during which the coumarin moieties were cleaved from the CMCS backbone, resulting in a shift of the hydrophilic–hydrophobic balance and destabilization of the micelles. Additionally, bioassay studies suggested that this 2,4-D contained which micelles showed good bioactivity on the target plant without harming the nontarget plant. Thereby, the light-responsive CMCS-DEACMS micelles bearing photocleavable coumarin moieties provide a smart delivery platform for agrochemicals.

Near-Infrared Light Laser-Triggered Release of Doxorubicin and Sorafenib from TemperatureSensitive Liposomes for Synergistic Therapy of Hepatocellular Carcinoma.

Chemotherapy of hepatocellular carcinoma (HCC) is facing drug resistance, which leads to unsatisfactory therapeutic effect. Thus, a combination therapy using multiple drugs may overcome this challenge. The current study aims to realize a synergistic chemotherapy of HCC by using a near-infrared light (NIR) responsive nanocarrier to co-deliver the chemotherapeutic drug Doxorubicin (DOX) and molecular targeting agent Sorafenib (SF). The nanocarrier, which could effectively load DOX in its aqueous core while SF and IR-780 in its lipid bilayer, is fabricated from a temperature-sensitive liposome (TSL) modified with PF127. An efficient SF and DOX co-loading was achieved, and meanwhile the effective photothermal conversion of IR-780 under NIR laser may cause a disassembly of the liposome structure which may trigger a rapid drug release in tumor site, greatly boosting the synergetic chemotherapeutic effect. The NIR laser-triggered drug release and the synergistic anti-tumor effect were evaluated both in cell and animal experiments, which revealed that the PF127-modified TSL is a potent nanoplatform to improve the HCC treatment through co-delivering a drug combination.

Polymeric Self-Assemblies Based on tetra-ortho-Substituted Azobenzene as Visible Light Responsive Nanocarriers.

Most of reported polymeric light-responsive nanocarriers make use of UV light to trigger morphological changes and the subsequent release of encapsulated cargoes. Moving from UV- to visible-responsive units is interesting for the potential biomedical applications of these materials. Herein we report the synthesis by ring opening polymerization (ROP) of a series of amphiphilic diblock copolymers, into which either UV or visible responsive azobenzenes have been introduced via copper(I) catalyzed azide-alkyne cycloaddition (CuAAC). These copolymers are able to self-assemble into spherical micelles or vesicles when dispersed in water. The study of the response of the self-assemblies upon UV (365 nm) or visible (530 or 625 nm) light irradiation has been studied by Transmission Electron Microscopy (TEM), Cryogenic Transmission Electron Microscopy (Cryo-TEM), and Dynamic Light Scattering (DLS) studies. Encapsulation of Nile Red, in micelles and vesicles, and Rhodamine B, in vesicles, and its light-stimulated release has been studied by fluorescence spectroscopy and confocal microscopy. Appreciable morphological changes have been induced with green light, and the subsequent release of encapsulated cargoes upon green light irradiation has been confirmed.

Remote Light-Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives.

Engineering of smart photoactivated nanomaterials for targeted drug delivery systems (DDS) has recently attracted considerable research interest as light enables precise and accurate controlled release of drug molecules in specific diseased cells and/or tissues in a highly spatial and temporal manner. In general, the development of appropriate light-triggered DDS relies on processes of photolysis, photoisomerization, photo-cross-linking/un-cross-linking, and photoreduction, which are normally sensitive to ultraviolet (UV) or visible (Vis) light irradiation. Considering the issues of poor tissue penetration and high phototoxicity of these high-energy photons of UV/Vis light, recently nanocarriers have been developed based on light-response to low-energy photon irradiation, in particular for the light wavelengths located in the near infrared (NIR) range. NIR light-triggered drug release systems are normally achieved by using two-photon absorption and photon upconversion processes. Herein, recent advances of light-responsive nanoplatforms for controlled drug release are reviewed, covering the mechanism of light responsive small molecules and polymers, UV and Vis light responsive nanocarriers, and NIR light responsive nanocarriers. NIR-light triggered drug delivery by two-photon excitation and upconversion luminescence strategies is also included. In addition, the challenges and future perspectives for the development of light triggered DDS are highlighted.

Exploring Light-Sensitive Nanocarriers for Simultaneous Triggered Antibiotic Release and Disruption of Biofilms Upon Generation of Laser-Induced Vapor Nanobubbles.

Impaired penetration of antibiotics through bacterial biofilms is one of the reasons for failure of antimicrobial therapy. Hindered drug diffusion is caused on the one hand by interactions with the sticky biofilm matrix and on the other hand by the fact that bacterial cells are organized in densely packed clusters of cells. Binding interactions with the biofilm matrix can be avoided by encapsulating the antibiotics into nanocarriers, while interfering with the integrity of the dense cell clusters can enhance drug transport deep into the biofilm. Vapor nanobubbles (VNB), generated from laser irradiated nanoparticles, are a recently reported effective way to loosen up the biofilm structure in order to enhance drug transport and efficacy. In the present study, we explored if the disruptive force of VNB can be used simultaneously to interfere with the biofilm structure and trigger antibiotic release from light-responsive nanocarriers. The antibiotic tobramycin was incorporated in two types of light-responsive nanocarriers—liposomes functionalized with gold nanoparticles (Lip-AuNP) and graphene quantum dots (GQD)—and their efficacy was evaluated on Pseudomonas aeruginosa biofilms. Even though the anti-biofilm efficacy of tobramycin was improved by liposomal encapsulation, electrostatic functionalization with 70 nm AuNP unfortunately resulted in premature leakage of tobramycin in a matter of hours. Laser-irradiation consequently did not further improve P. aeruginosa biofilm eradication. Adsorption of tobramycin to GQD, on the other hand, did result in a stable formulation with high encapsulation efficiency, without burst release of tobramycin from the nanocarriers. However, even though laser-induced VNB formation from GQD resulted in biofilm disruption, an enhanced anti-biofilm effect was not achieved due to tobramycin not being efficiently released from GQD. Even though this study was unsuccessful in designing suitable nanocarriers for simultaneous biofilm disruption and light-triggered release of tobramycin, it provides insights into the difficulties and challenges that need to be considered for future developments in this regard.

Visible light-triggered cargo release from donor acceptor Stenhouse adduct (DASA)-doped lyotropic liquid crystalline nanoparticles

Light-responsive nanocarriers are applicable as non-invasive, highly tunable and precisely controlled drug delivery systems. Here, we report a new nanocarrier system, achieved by doping D1, a type of green light–responsive donor acceptor Stenhouse adduct (DASA), into a lipid-based lyotropic liquid crystalline system. Time-resolved small angle X-ray scattering was used to confirm that the matrix underwent a rapid and fully reversible phase transition from lamellar to inverse cubic phase upon irradiation with green light (532 nm), reverting back on removal of light. Fluorescein isothiocyanate–dextran (FD4) was used as a model hydrophilic cargo. The release of cargo upon varying irradiation parameters was investigated in vitro which showed that irradiation can trigger a burst release of FD4 upon phase transition. This additive shows promise for the development of new visible light-activated, “on demand” drug delivery systems.

The design and synthesis of a photo-controlled, peptide-based potential drug carrier

Our focus in this study is on the design and synthesis of a light-responsive peptide-based nanocarrier in order to develop effective and biocompatible drug delivery systems. The synthesized nanocarrier is basically composed of peptide amphiphiles comprising a micelle forming a Pro-Pro-Pro-Lys-Lys-Lys peptide sequence with an attached anthracene fluorophore. Anthracene containing an inner core of the micelle can serve as a storage site for poorly water-soluble drugs. Moreover, anthracenes that come in close proximity with the formation of micellar structures can undergo photodimerization upon irradiation at 365 nm, which disrupts the micelle structures formed by the self-assembly of the peptide amphiphiles. Therefore, if a drug is encapsulated within the hydrophobic core of this peptidic carrier system, its release can be induced by the controlled exposure of the anthracene moiety to UV light.

Photoswitchable Molecules in Long-Wavelength Light-Responsive Drug Delivery: From Molecular Design to Applications

Stimuli-responsive nanocarriers can release their bioactive cargo “on demand”, potentially improving the selectivity, specificity, and efficacy of therapeutic drugs. Light of wavelengths between 650–1100 nm is a unique stimulus with many advantages. It is noninvasive and “bio-friendly” and can be manipulated with precision and ease. Many light-responsive nanocarriers reported in the literature employ photochromic molecules that undergo reversible isomerization upon irradiation, thereby functioning as gates or switches for the release of encapsulated bioactive compounds. This review surveys the design, synthesis, function, and application of one-photon visible and near-infrared light-triggered photoswitchable compounds in the development of long-wavelength light-responsive nanocarriers.

Near-infrared light-triggered drug release from UV-responsive diblock copolymer-coated upconversion nanoparticles with high monodispersity.

The preparation of a new near-infrared (NIR) light-responsive nanocarrier for controlled drug release is demonstrated. Upconversion nanoparticles (UCNPs) were coated with an amphiphilic diblock copolymer through surface-initiated atom transfer radical polymerization, in which the inner block is hydrophobic, ultraviolet (UV)-sensitive poly(4,5-dimethoxy-2-nitrobenzyl methacrylate) (PNB), and the outer block is hydrophilic poly(methoxy polyethylene glycol monomethacrylate) (POEG). The resulting polymer/UCNP nanocarrier is thermally stable in water over a wide temperature range (5-70 °C) and is uniform in size (120 nm hydrodynamic diameter, polydispersity index <0.1). The diblock copolymer self-assembly on the surface of each UCNP occurs in aqueous solution, which allows encapsulation of antitumor drugs like doxorubicin (DOX) by the hydrophobic "micelle-like" core of PNB surrounding the NIR-sensitive UCNP. Under 980 nm laser exposure, the UV light emitted by the single UCNP is absorbed by the PNB inner layer, which results in cleavage of o-nitrobenzyl groups and formation of carboxylic acid groups. The increasing hydrophilicity of the diblock copolymer resulting from the NIR light-triggered photochemical reaction can thus disrupt the nanocarrier and leads to the release of DOX molecules. This diblock copolymer self-assembly-based approach to constructing NIR light-responsive nanocarriers of well-defined structures is general and offers possibilities for photocontrolled drug delivery.

Affinity-Based Assembly of Peptides on Plasmonic Nanoparticles Delivered Intracellularly with Light Activated Control.

We report a universal strategy for functionalizing near-infrared light-responsive nanocarriers with both a peptide "cargo" and an orthogonal cell-penetrating peptide. Modularity of both the cargo and the internalization peptide attachment is an important feature of these materials relying on the robust affinity of polyhistidine tags to nitrilotriacetic acid in the presence of nickel as well as the affinity of biotin labeled peptides to streptavidin. Attachment to the gold surface uses thiol-labeled scaffolds terminated with the affinity partner. These materials allow for unprecedented spatiotemporal control over the release of the toxic α-helical amphipathic peptide (KLAKLAK)2 which disrupts mitochondrial membranes and initiates apoptotic cell death. Laser treatment at benign near-infrared wavelengths releases peptide from the gold surface as well as breaches the endosome barrier for cytosolic activity (with 105-fold improved response to peptide activity over the free peptide) and can be monitored in real time.

PH- and NIR light responsive nanocarriers for combination treatment of chemotherapy and photodynamic therapy.

The side effects of antitumor drugs and low treatment efficacy are two major challenges of current chemotherapy. To address these issues, we developed a new kind of smart nanocarriers that combine pH-responsive chemotherapy and near-infrared (NIR) light triggered photodynamic therapy. These nanocarriers were based on upconversion nanoparticle (UCN)-loaded folate-conjugated polymeric lipid vesicles (UFPLVs). Merocyanine 540 (MC540), as a photosensitizer, was loaded in the UFPLVs; doxorubicin hydrochloride (DOX), as an antitumor drug, was conjugated to the surfaces of UFPLVs by pH-sensitive hydrazone bonds. The newly developed MC540&DOX-UFPLVs had a nanosized structure with targeting ligand modification, so they had the potential to accumulate into tumor sites via a combination of passive and active targeting effects. An in vitro singlet oxygen test showed that the nanocarriers can generate cytotoxic singlet oxygen successfully under the irradiation of NIR light. In vitro DOX release profiles demonstrated that the nanocarriers can achieve a pH-triggered drug release. It has been demonstrated by a cellular uptake study that the nanocarriers can efficiently deliver drugs and photosensitizers into tumor cells. In vitro and in vivo combination treatments evidenced the high antitumor effects of MC540&DOX-UFPLVs under NIR light irradiation. These results suggest that the MC540&DOX-UFPLVs may be promising nanocarriers for tumor combination therapy applications.