Facile synthesis of size-tunable stable nanoparticles via click reaction for cancer drug delivery

The stability and size of polymeric nanoparticles are two of the most important parameters determining their pharmacokinetics and tumor/drug accumulation efficiency in cancer-drug delivery. Herein, we report a facile one-pot synthesis of crosslinked nanoparticles (CNPs) with tunable sizes and polyethylene glycol (PEG) shells via click reactions. Simply by adjusting the contents of the macromonomer (PEG monoacrylate) in its reaction with ethylene diacrylate and a crosslinker containing hexa-thiols groups, the sizes of the resulting PEGylated crosslinked nanoparticles could be easily tuned from 10 to 90 nm. These nanoparticle cores could encapsulate hydrophobic drugs such as doxorubicin (DOX), and the unreacted thiol and acrylate groups could be used for drug conjugation or labeling. Thus, the nanoparticles provide a multifunctional platform for drug delivery. In vivo studies showed that the larger nanoparticles (about 83.7 nm) had a much longer blood-circulation time and better tumor-targeting efficiency. One of our most important findings was that the drug encapsulated in the crosslinked nanoparticles, even though little was released at pH 7.4 under in vitro conditions, had much faster blood clearance than the nanoparticles’ carrier, suggesting that drug release in the bloodstream was significant.     

Oral delivery of polyester nanoparticles for brain-targeting: Challenges and opportunities

Efficient oral delivery of drugs treating brain diseases has long been a challenging topic faced by the drug delivery community. Fortunately, polyester nanoparticles offer certain solutions to this problem. This review article firstly describes the main obstacles faced by oral administered brain targeting, including:(1)instability in the gastrointestinal tract;(2) poor penetration of the intestinal mucosa and epithelium;(3)blood clearance; and(4) restriction by the BBB. Then the key factors infl...     

Effects of polymer molecular weight on in vitro and in vivo performance of nanoparticle drug carriers for lymphoma therapy

The clinical efficacy of chemotherapeutic drugs is hindered by their poor aqueous solubility, low bioavailability and severe side effects. In recent years, polymeric nanocarriers have been used for drug delivery to improve the efficacy of many chemotherapeutics. In this study, a series of biodegradable phenylalanine-based poly(ester amide) (Phe-PEA) with tunable molecular weights (MWs) were synthesized to systematically investigate the relationship between the polymer MW and the efficacy of the corresponding polymeric nanoparticles (NPs). The results indicated that a range of polymers with different MWs can be obtained by varying the monomer ratio or reaction time. Doxorubicin (DOX), a classic clinical lymphoma treatment strategy, was selected as a model drug. The loading capacity and stability of the higher MW polymeric NPs were superior to those of the lower MW ones. Moreover, in vitro and in vivo data revealed that high MW polymeric NPs had better anticancer efficacy against lymphoma and higher biosafety than low MW polymeric nanoparticles and DOX. Therefore, this study suggests the importance of polymer MW for drug delivery systems and provides valuable guidance for the design of enhanced polymeric drug carriers for lymphoma treatment.     

Co-delivery of anticancer drugs and cell penetrating peptides for improved cancer therapy

Delivery systems based on nanoparticles (NPs) have shown great potential to reduce side effects and improve the therapeutic efficacy. Herein, we report the one-pot synthesis of poly(ethylene glycol)-mediated zeolitic imidazolate framework-8 (ZIF-8) NPs for the co-delivery of an anticancer drug (i.e., doxorubicin) and a cell penetrating peptide containing histidine and arginine (i.e., H4R4) to improve the efficacy of therapeutic delivery. The cargo-encapsulated ZIF-8 NPs are pH-responsive, which are stable at neutral pH and degradable at acidic pH to release the encapsulated cargos. The released H4R4 can help for endosome/lysosome escape to enhance the cytotoxicity of the encapsulated drugs. In vivo studies demonstrate that the co-delivery of doxorubicin and H4R4 peptides can efficiently inhibit tumor growth without significant side effects. The reported strategy provides a new perspective on the design of drug delivery systems and brings more opportunities for biomedical applications.     

Design and Characterization of Maltoheptaose-b-Polystyrene Nanoparticles,as a Potential New Nanocarrier for Oral Delivery of Tamoxifen

Tamoxifen citrate (TMC), a non-steroidal antiestrogen drug used for the treatment of breast cancer, was loaded in a block copolymer of maltoheptaose-b-polystyrene (MH-b-PS) nanoparticles, a potential drug delivery system to optimize oral chemotherapy. The nanoparticles were obtained from self-assembly of MH-b-PS using the standard and reverse nanoprecipitation methods. The MH-b-PS@TMC nanoparticles were characterized by their physicochemical properties, morphology, drug loading and encapsulation efficiency, and release kinetic profile in simulated intestinal fluid (pH 7.4). Finally, their cytotoxicity towards the human breast carcinoma MCF-7 cell line was assessed. The standard nanoprecipitation method proved to be more efficient than reverse nanoprecipitation to produce nanoparticles with small size and narrow particle size distribution. Moreover, tamoxifen-loaded nanoparticles displayed spherical morphology, a positive zeta potential and high drug content (238.6 ± 6.8 µg mL⁻¹) and encapsulation efficiency (80.9 ± 0.4 %). In vitro drug release kinetics showed a burst release at early time points, followed by a sustained release profile controlled by diffusion. MH-b-PS@TMC nanoparticles showed higher cytotoxicity towards MCF-7 cells than free tamoxifen citrate, confirming their effectiveness as a delivery system for administration of lipophilic anticancer drugs.     

Semi-elastic core-shell nanoparticles enhanced the oral bioavailability of peptide drugs

The rigidity of nanoparticles was newly reported to influence their oral delivery. Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells. However, it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide drugs. This study was for the first time to validate the semi-elastic core-shell poly(lactic-co-glycolic acid) (PLGA)-lipid nanoparticles (LNPs) as the carrier of the oral peptide drug. The antihypertensive peptide Val-Leu-Pro-Val-Pro (VP5) loaded LNPs (VP5-LNPs) were prepared by a modified thin-film ultrasonic dispersion method. Uptake experiment was performed in Caco-2 and HT-29 cells and monitored by high content screening (HCS) and flow cytometric (FCM). Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley (SD) rats and analyzed by DAS 2.0. The optimal VP5-LNPs had an average particle size of 247.3 ± 3.8 nm, zeta potential of −6.57 ± 0.45 mV and excellent entrapment efficiency (EE) of 89.88% ± 1.23%. Transmission electron microscope (TEM) and Differential scanning calorimeter (DSC) further confirmed the core-shell structure. VP5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72 h, indicating a great promotion of the oral bioavailability. The semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.     

Facile preparation of pH-responsive PEGylated prodrugs for activated intracellular drug delivery

PEGylated prodrug, covalent attaching polyethylene glycol (PEG) polymer chains to therapeutic drugs, is one of the most promising techniques to improve the water-solubility, stability, and therapeutic effect of drugs. In this study, three PEGylated acid-sensitive prodrugs DOX-PEG-DOX with different molecular weights, were prepared via Schiff-base reaction between aldehyde-modified PEG and the amino groups of doxorubicin (DOX). This kind of amphiphilic polymeric prodrug could be self-assemble into nanoparticles in aqueous solution. The average particle size and morphologies of the prodrug nanoparticles under different pH conditions were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. It turned out that the nanoparticles could be kept stable in the physiological environment, but degraded in acidic medium. Subsequently, we also investigated in vitro drug release behavior and found that the prodrug had acid-sensitive property. The cytotoxicity and intracellular uptake assays revealed that the prodrugs could rapidly internalized by HeLa or HepG2 cells to release DOX and effectively inhibited the proliferation of the tumor cells, which have the potential for use in cancer therapy.     

Formulation of Tioconazole and Melaleuca alternifolia Essential Oil Pickering Emulsions for Onychomycosis Topical Treatment

Onychomycosis is a disease that affects many adults, whose treatment includes both oral and topical therapies with low cure rates. The topical therapy is less effective but causes fewer side effects. This is why the development of an effective, easy to apply formulation for topical treatment is of high importance. We have used a nanotechnological approach to formulate Pickering emulsions (PEs) with well-defined properties to achieve site-specific delivery for antifungal drug combination of tioconazole and Melaleuca alternifolia essential oil. Silica nanoparticles with tailored size and partially hydrophobic surface have been synthesized and used for the stabilization of PEs. In vitro diffusion studies have been performed to evaluate the drug delivery properties of PEs. Ethanolic solution (ES) and conventional emulsions (CE) have been used as reference drug formulations. The examination of the antifungal effect of PEs has been performed on Candida albicans and Trichophyton rubrum as main pathogens. In vitro microbiological experimental results suggest that PEs are better candidates for onychomycosis topical treatment than CE or ES of the examined drugs. The used drugs have shown a significant synergistic effect, and the combination with an effective drug delivery system can result in a promising drug form for the topical treatment of onychomycosis.     

Role of surface-exposed charged basic amino acids (Lys,Arg) and guanidination in insulin on the interaction and stability of insulin–insulin receptor complex

Naturally occurring proteins are emerging as novel therapeutics in the protein-based biopharmaceutical industry for the treatment of diabetes and obesity. However, proteins are not suitable for oral delivery due to short half-life, reduced physical and chemical stability and low permeability across the membrane. Chemical modification has been identified as a formulation strategy to enhance the stability and bioavailability of protein drugs. The present study aims to study the effect of charge-specific modification of basic amino acids (Lys, Arg) and guanidination on the interaction of insulin with its receptor using molecular modelling. Our investigation revealed that the guanidination of insulin (Lys-NHC = NHNH₂) enhanced and exerted stronger binding of the protein to its receptor through electrostatic interaction than native insulin (Lys-NH₃⁺). Point mutations of Lys and Arg (R22, K29; R22K, K29; R22, K29R; R22K, K29R) were attempted and the effects on the interaction and stability between insulin/modified insulins and insulin receptor were also analyzed in this study. The findings from the study are expected to provide a better understanding of the possible mechanism of action of the modified protein at a molecular level before advancing to real experiments.     

Co-delivery of doxorubicin and paclitaxel with linear-dendritic block copolymer for enhanced anti-cancer efficacy

A series of well-defined amphiphilic linear-dendritic block copolymers (telodendrimers, MPEG-b-PAMAM-cholesterol) with 1,2,4 or 8 cholesteryl groups (named as P1, P2, P4, P8, respectively) were synthesized. Their chemical structures were characterized with ¹H NMR and mass spectrum (MALDI-TOF MS). The telodendrimers could self-assemble into micelles in aqueous solution, and encapsulate chemotherapeutic drug doxorubicin (DOX) and paclitaxel (PTX) for combination therapy. All the telodendrimers could encapsulate DOX with similar capability. However, their drug-loading capability of PTX is increased with the increasing number of cholesteryl groups. P8 exhibited much higher PTX loading efficiency than its counterparts. Thus, P8 was selected for further application of drug delivery in the paper. The drug-loading micellar nanoparticles (NPs) of P8 were spherical in shape and their diameters were less than 150 nm which were determined by dynamic light scattering measurements (DLS) and transmission electron microscope (TEM). In vitro drug release experiment demonstrated that P8 exhibited a controlled release manner for both DOX and PTX, and the two drugs were released simultaneously. In vitro cytotoxicity experiment further demonstrated that the co-delivery of DOX and PTX in P8 exhibited better anti-cancer efficiency than the delivery systems encapsulated with single drug (DOX or PTX). This indicates a synergistic effect. The co-delivery system showed potential in future anti-cancer treatment.     

Oral colon-targeted mucoadhesive micelles with enzyme-responsive controlled release of curcumin for ulcerative colitis therapy

Although multitudinous nanoscale drug-delivery systems (DDSs) have been recommended to improve anti-ulcerative colitis (UC) outcomes, to enhance the mucoadhesion of nanosystems on the colon and specifically release the loaded drugs in response to the colon micro-environment would be critical factors. The application of curcumin (Cur), an acknowledged anti-UC phytochemical compound, for UC therapy requires more efficient nano-carriers to improve its therapeutic outcome. Herein, we developed the colon-targeted nano-micelles with mucoadhesive effect and Azo reductase-triggered drug release profiles for Cur delivery in UC treatment. Specifically, the amphiphilic block polymer containing the Azo-reductase sensitive linkage (PEG-Azo-PLGA), and catechol-modified TPGS (Cat-TPGS) were synthesized respectively. Based on the self-assembly of the mixed polymers, Cur-micelles (142.7 ± 1.7 nm of average size, 72.36% ± 1.54% of DEE) were obtained. Interestingly, the Cur-micelles exhibited the Azo-reductase sensitive particle dissociation and drug release, the enhanced cellular uptake and the prolonged retention on colonic mucosa, mediated by the strong mucoadhesion of catechol structure. Ultimately, Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors (MPO, IL-6, IL-1β, and TNF-α) related to TLR4/MyD88/NF-κB signaling pathway. This work provides an effective drug delivery strategy for anti-UC drugs by oral administration.     

Dual-labeled visual tracer system for topical drug delivery by nanoparticle-triggered P-glycoprotein silencing

Using nanoparticle-based drug delivery systems as enhancers is a robust strategy for transdermal delivery; however, the mechanisms by which these systems promote transdermal penetration are still unclear. Here, we fabricated a dual-labeled nano drug delivery system that allows discrete visualization of both the drug and the nanoparticle carrier. To comprehensively examine its potential mechanism, we investigated its effects on human epidermal keratinocyte HaCaT cells, including changes in cell membrane potential, intracellular Ca²⁺ concentration, and Ca²⁺-ATPase activity. P-glycoprotein (P-gp) expression in nanoparticle-treated human dermal microvascular endothelial cells was detected by western blotting and immunofluorescence. Furthermore, the transdermal absorption and biodistribution of the dual-labeled nanoparticles were deeply investigated by skin permeability study in vitro and in vivo using fluorescence microscopy and in vivo imaging, respectively. In addition to reducing membrane potential, increasing the intracellular Ca²⁺ concentration, and decreasing Ca²⁺-ATPase activity, our results indicate that the dual-labeled nanoparticles can downregulate P-gp to promote transdermal absorption. Fluorescence and in vivo imaging visually demonstrated that the nanoparticle delivery system penetrated into the dermis through the stratum corneum. All these results indicate that this dual-labeled nano delivery system provides a new method for future in-depth visual explorations of transdermal drug delivery mechanisms.     

Studies on antineoplastic effect by adjusting ratios of targeted-ligand and antitumor drug

A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid(GA) and doxorubicin(DOX) conjugates at different ratios. GA(a liver-targeting ligand) and DOX(an antitumor drug) were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate(ALG-mOEG) for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1:1(W:W) ratio of GA-ALG-mOEG and DOXALG-mOEG(NPs-3) showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and antitumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth(88.37% reduction in tumor weight) 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.     

Enhancing Tumor Cell Response to Chemotherapy through the Targeted Delivery of Platinum Drugs Mediated by Highly Stable,Multifunctional Carboxymethylcellulose‐Coated Magnetic Nanoparticles

The fabrication of nanoparticles using different formulations, and which can be used for the delivery of chemotherapeutics, has recently attracted considerable attention. We describe herein an innovative approach that may ultimately allow for the selective delivery of anticancer drugs to tumor cells by using an external magnet. A conventional antitumor drug, cisplatin, has been incorporated into new carboxymethylcellulose‐stabilized magnetite nanoparticles conjugated with the fluorescent marker Alexa Fluor 488 or folic acid as targeting agent. The magnetic nanocarriers possess exceptionally high biocompatibility and colloidal stability. These cisplatin‐loaded nanoparticles overcome the resistance mechanisms typical of free cisplatin. Moreover, experiments aimed at the localization of the nanoparticles driven by an external magnet in a medium that mimics physiological conditions confirmed that this localization can inhibit tumor cell growth site‐specifically.     

Selenized liposomes with ameliorative stability that achieve sustained release of emodin but fail in bioavailability

Stability of liposomes plays a crucial role in drug delivery, especially in oral aspect. The structural modification of liposomes has been the orientation of efforts to improve their stability and enable the controllability of payload release. This study reported a selenylation strategy to optimize the liposomal structure in an attempt to enhance the nanocarrier's stability, hence the bioavailability of emodin (EM), an active compound with poor water-solubility. EM-loaded selenized liposomes (EM-Se@LPs) were prepared by thin film dispersion followed by in situ reduction technique. The results showed that EM-Se@LPs were provided with enhancive gastrointestinal stability and exhibited sustained release of drug compared with EM-loaded liposomes (EM-LPs). However, the modified liposomes with Se depositing onto the interior and exterior bilayers did not substantially facilitate absorption of EM. The reinforced structure of liposomes irrelevant to absorption was affirmed to be due to good stability and absorbability of EM itself. Nevertheless, the present work provides an alternative option for stabilization of liposomes instead of conventional methods, which may be promising for oral delivery of physiologically unstable and/or poorly absorbed drugs and systemic drug delivery.     

Biocompatible APTES–PEG Modified Magnetite Nanoparticles: Effective Carriers of Antineoplastic Agents to Ovarian Cancer

Magnetite nanoparticles are particularly attractive for drug delivery applications because of their size-dependent superparamagnetism, low toxicity, and biocompatibility with cells and tissues. Surface modification of iron oxide nanoparticles with biocompatible polymers is potentially beneficial to prepare biodegradable nanocomposite-based drug delivery agents for in vivo and in vitro applications. In the present study, the bare (10 nm) and polyethylene glycol (PEG)–(3-aminopropyl)triethoxysilane (APTES) (PA) modified (17 nm) superparamagnetic iron oxide nanoparticles (SPIO NPs) were synthesized by coprecipitation method. The anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately encapsulated into the synthesized polymeric nanocomposites for localized targeting of human ovarian cancer in vitro. Surface morphology analysis by scanning electron microscopy showed a slight increase in particle size (27?±?0.7 and 30?±?0.45 nm) with drug loading capacities of 70 and 61.5 % and release capabilities of 90 and 93 % for the DOX- and PTX-AP-SPIO NPs, respectively (p?<?0.001). Ten milligrams/milliliter DOX- and PTX-loaded AP-SPIO NPs caused a significant amount of cytotoxicity and downregulation of antiapoptotic proteins, as compared with same amounts of free drugs (p?<?0.001). In vivo antiproliferative effect of present formulation on immunodeficient female Balb/c mice showed ovarian tumor shrinkage from 2,920 to 143 mm³ after 40 days. The present formulation of APTES–PEG-SPIO-based nanocomposite system of targeted drug delivery proved to be effective enough in order to treat deadly solid tumor of ovarian cancer in vitro and in vivo.     

Fluorescent AIE dots encapsulated organically modified silica (ORMOSIL) nanoparticles for two-photon cellular imaging

2,3-Bis(4-(phenyl(4-(1,2,2-triphenylvinyl)phenyl)amino)phenyl) fumaronitrile (TPE-TPA-FN or TTF), which possesses aggregation-induced emission (AIE) characteristic, is doped in organically modified silica (ORMOSIL) nanoparticles. By increasing the weight ratio of TTF to the precursor of silica nanoparticles (the quantities of the precursors were kept the same), the fluorescence intensity of nanoparticles increased correspondingly, due to the formation of larger AIE dots in the cores of ORMOSIL nanoparticles. The fluorescent and biocompatible nanoprobes were then utilized for in vitro imaging of HeLa cells. Two-photon fluorescence microscopy clearly illustrated that the nanoparticles have the capacity of nucleus permeability, as well as cytoplasm staining towards tumor cells. Our experimental results may offer a promising method for fast and bright fluorescence imaging, as well as bio-molecule/drug delivery to cell nucleus.     

Mesoporous silica nanoparticles for 19F magnetic resonance imaging,fluorescence imaging,and drug delivery

Multifunctional mesoporous silica nanoparticles (MSNs) are good candidates for multimodal applications in drug delivery, bioimaging, and cell targeting. In particular, controlled release of drugs from MSN pores constitutes one of the superior features of MSNs. In this study, a novel drug delivery carrier based on MSNs, which encapsulated highly sensitive ¹⁹F magnetic resonance imaging (MRI) contrast agents inside MSNs, was developed. The nanoparticles were labeled with fluorescent dyes and functionalized with small molecule-based ligands for active targeting. This drug delivery system facilitated the monitoring of the biodistribution of the drug carrier by dual modal imaging (NIR/¹⁹F MRI). Furthermore, we demonstrated targeted drug delivery and cellular imaging by the conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin, DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug delivery. The release rates of DOX from the nanoparticles increased under acidic conditions, and were favorable for controlled drug release to cancer cells. Our results suggested that MSNs may serve as promising ¹⁹F MRI-traceable drug carriers for application in cancer therapy and bio-imaging.     

Identification of the polymorphisms in IFITM3 gene and their association in a Korean population with ulcerative colitis

Interferons play critical roles in tumor pathogenesis by controlling apoptosis and through cellular anti-proliferative and differentiation activities. Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFN and cellular anti-proliferative activities. Expression levels of IFITM genes have been found to be up-regulated in gastric cancer cells and colorectal tumors. IFITM3 (also known as 1-8U) is a member of the IFITM family, and has been described as a key player in specification of germ cell fate. IFITM3 was first isolated from a genetic screen aimed at identifying genes involved in acquisition of germ cell competence. It has been proposed that epiblast cells have the highest expression of IFITM3 initiated germ cell specification and that homotypic association can discriminate germ cells from their somatic neighbors. In an attempt to better understand the genetic influences of IFITM3 on ulcerative colitis, we have identified possible variation sites and single nucleotide polymorphisms (SNPs) through two exons and their boundary IFITM3 intron sequences including the ~2.1 kb promoter regions. To determine whether or not these IFITM3 SNPs are associated with susceptibility to ulcerative colitis, frequencies of the genotype and allele of IFITM3 polymorphisms were analyzed on genomic DNAs isolated from patients with ulcerative colitis and from healthy controls. We also investigated the haplotype frequencies constructed by these SNPs in both groups. In this study, we also showed that expression level of IFITM3 mRNA was significantly higher in tissues of the ileum and cecum of the digestive system. We identified a total of seven SNPs and multiple variation regions in the IFITM3 gene. The genotype frequency of the g.-204T>G polymorphism in patients with ulcerative colitis was significantly different from that of the control group. Our results strongly suggest that polymorphisms of the IFITM3 gene may be associated with susceptibility to ulcerative colitis.     

NIR light-induced tumor phototherapy using ICG delivery system based on platelet-membrane-camouflaged hollow bismuth selenide nanoparticles

Near-infrared (NIR) light-triggered photothermal therapy (PTT) is a promising treatment strategy for treating cancer. The combination of nanotechnology and NIR has been widely applied. However, the therapeutic efficacy of the drug-delivery system depends on their ability to avoid phagocytosis of endothelial system, cross the biological barriers, prolong circulation life, localize and rapidly release the therapeutic at target sites. In this work, we designed a platelet membrane (PM)-camouflaged hollow mesoporous bismuth selenide nanoparticles (BS NPs) loading with indocyanine green (ICG) (PM@BS-ICG NPs) to achieve the above advantages. PM-coating has active tumor-targeting ability which could prevent drug leakage and provide drug long circulation, causing drug delivery systems to accumulate in tumor sites effectively. Moreover, as a type of the photothermal sensitizers, BS NPs are used as the inner cores to improve ICG stability and are served as scaffolds to enhance the hardness of this drug delivery system. For one hand, the thermal vibration of BS NPs under NIR laser irradiation causes tumor inhibition through hyperthermia. For another hand, this hyperthermia process could damage PM and let ICG rapid release from PM@BS-ICG NPs. The in vitro and in vivo results showed that this biomimetic nano-drug delivery system exhibits obvious antitumor activity which has good application prospect.