Model‐Based Nanoengineered Pharmacokinetics of Iron‐Doped Copper Oxide for Nanomedical Applications

The progress in nanomedicine (NM) using nanoparticles (NPs) is mainly based on drug carriers for the delivery of classical chemotherapeutics. As low NM delivery rates limit therapeutic efficacy, an entirely different approach was investigated. A homologous series of engineered CuO NPs was designed for dual purposes (carrier and drug) with a direct chemical composition–biological functionality relationship. Model‐based dissolution kinetics of CuO NPs in the cellular interior at post‐exposure conditions were controlled through Fe‐doping for intra/extra cellular Cu²⁺ and biological outcome. Through controlled ion release and reactions taking place in the cellular interior, tumors could be treated selectively, in vitro and in vivo. Locally administered NPs enabled tumor cells apoptosis and stimulated systemic anti‐cancer immune responses. We clearly show therapeutic effects without tumor cells relapse post‐treatment with 6 % Fe‐doped CuO NPs combined with myeloid‐derived suppressor cell silencing.     

Hyperbranched copolymer micelles as delivery vehicles of doxorubicin in breast cancer cells

Four types of drug nanoparticles (NPs) based on amphiphilic hyperbranched block copolymers were developed for the delivery of the chemotherapeutic doxorubicin (DOX) to breast cancer cells. These carriers have their hydrophobic interior layer composed of the hyperbranched aliphatic polyester, Boltorn^® H30 or Boltorn^® H40, that are polymers of poly 2,2‐bis (methylol) propionic acid (bis‐MPA), while the outer hydrophilic shell was composed of about 5 poly(ethylene glycol) (PEG) segments of 5 or 10 kDa molecular weight. A chemotherapeutic drug DOX, was further encapsulated in the interior of these polymer micelles and was shown to exhibit a controlled release profile. Dynamic light scattering and transmission electron microscopy analysis confirmed that the NPs were uniformly sized with a mean hydrodynamic diameter around 110 nm. DOX‐loaded H30‐PEG10k NPs exhibited controlled release over longer periods of time and greater cytotoxicity compared with the other materials developed against our tested breast cancer cell lines. Additionally, flow cytometry and confocal scanning laser microscopy studies indicated that the cancer cells could internalize the DOX‐loaded H30‐PEG10k NPs, which contributed to the sustained drug release, and induced more apoptosis than free DOX did. These findings indicate that the H30‐PEG10k NPs may offer a very promising approach for delivering drugs to cancer cells. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Green synthesis of Zn nanoparticles and in situ hybridized with BSA nanoparticles for Baicalein targeted delivery mediated with glutamate receptors to U87-MG cancer cell lines

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the brain. It has different glutamate receptor types. So, these receptors can be a suitable target for GBM treatment. The current study investigated the anticancer effects of bovine serum albumin (BSA)-Baicalein @Zn-Glu nanostructure mediated-GluRs in human glioblastoma U87 cells. BSA-Ba@Zn-Glu hybrid nanoparticles (NPs) were set and considered transporters for Baicalein (Ba) active compound delivery. BSA-Ba@Zn-Glu NPs were synthesized by a single-step reduction process. The successful production was confirmed through transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and hemolysis test. The cytotoxic efficacy and apoptosis rate of the nanostructures on U87 glioblastoma cells were investigated by 3-(4,5-dimethylthialzol-a-yl)-2,5 diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. The synthesized BSA-Ba@Zn-Glu nanostructures with a diameter of 142.40 ± 1.91 to 177.10 ± 1.87 nm and zeta potential of −10.57 ± 0.71 to −35.77 ± 0.60 mV are suitable for extravasation into tumor cells. The drug release from the BSA-Ba@Zn NPs showed controlled and pH-dependent behavior. In vitro results indicated that the BSA-Ba@Zn-Glu NPs significantly reduce cell viability and promote apoptosis of U87 cancer cells. It revealed the cytotoxic effect of the Baicalein and an increase in cellular uptake of nanoparticles by Glu receptors. Zn NPs were synthesized based on a green synthesis method. BSA NPs were used as a nano-platform for Glu conjugation and Ba drug delivery. BSA-Ba@Zn-Glu NPs induce cytotoxicity and apoptosis in human brain cancer cells (U87) in a dose-dependent manner. Finally, this nanostructure could be served in targeted drug delivery in vivo studies and applied along with other strategies such as X-ray irradiation as combinational therapies in future studies.     

Mussel‐Inspired Protein Nanoparticles Containing Iron(III)–DOPA Complexes for pH‐Responsive Drug Delivery

A novel bioinspired strategy for protein nanoparticle (NP) synthesis to achieve pH‐responsive drug release exploits the pH‐dependent changes in the coordination stoichiometry of iron(III)–3,4‐dihydroxyphenylalanine (DOPA) complexes, which play a major cross‐linking role in mussel byssal threads. Doxorubicin‐loaded polymeric NPs that are based on Fe^III–DOPA complexation were thus synthesized with a DOPA‐modified recombinant mussel adhesive protein through a co‐electrospraying process. The release of doxorubicin was found to be predominantly governed by a change in the structure of the Fe^III–DOPA complexes induced by an acidic pH value. It was also demonstrated that the fabricated NPs exhibited effective cytotoxicity towards cancer cells through efficient cellular uptake and cytosolic release. Therefore, it is anticipated that Fe^III–DOPA complexation can be successfully utilized as a new design principle for pH‐responsive NPs for diverse controlled drug‐delivery applications.     

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.     

Pericellular matrix plays an active role in retention and cellular uptake of large-sized nanoparticles

As the outmost coating of cells, the pericellular matrix (PCM) involved in various cellular functions has been exploited previously to be able to accumulate 120 nm Au nanoparticles (NPs), adjust their diffusion coefficient similar to that of membrane receptors, and enhance their uptake efficiency. In this study, the interactions between PCM and NPs with different sizes and materials were systematically investigated. We found that PCM can selectively enhance the retention and cellular uptake of NPs with diameters from 50 to 180 nm, but has no enhancement effect for 20 nm NPs. Identical behaviors of PCM was observed for both Au NPs and polystyrene NPs, indicating that this unique phenomenon is more related to the dimensions of the NPs. The study of single-particle tracking of 50–180 nm NPs on the surface of thick PCM cells revealed that PCM actively adjusts the diffusion coefficient of NPs to ～0.1 μm²/s regardless of their sizes. By blocking the receptor-mediated endocytosis (RME) pathway with four different inhibitors, this active role of PCM can be effectively suppressed, further confirming that the trapping and retention of NPs by PCM is an inherent biological function. These findings provided new insights for better understanding of the RME pathway and may have promising NP-based applications for controlled drug delivery and therapy in biomedicine.

Endosomal pH-Responsive Fe-Based Hyaluronate Nanoparticles for Doxorubicin Delivery

In this study, we report pH-responsive metal-based biopolymer nanoparticles (NPs) for tumor-specific chemotherapy. Here, aminated hyaluronic acid (aHA) coupled with 2,3-dimethylmaleic anhydride (DMA, as a pH-responsive moiety) (aHA-DMA) was electrostatically complexed with ferrous chloride tetrahydrate (FeCl₂/4H₂O, as a chelating metal) and doxorubicin (DOX, as an antitumor drug model), producing DOX-loaded Fe-based hyaluronate nanoparticles (DOX@aHA-DMA/Fe NPs). Importantly, the DOX@aHA-DMA/Fe NPs improved tumor cellular uptake due to HA-mediated endocytosis for tumor cells overexpressing CD44 receptors. As a result, the average fluorescent DOX intensity observed in MDA-MB-231 cells (with CD44 receptors) was ~7.9 × 10² (DOX@HA/Fe NPs, without DMA), ~8.1 × 10² (DOX@aHA-DMA_0.36/Fe NPs), and ~9.3 × 10² (DOX@aHA-DMA_0.60/Fe NPs). Furthermore, the DOX@aHA-DMA/Fe NPs were destabilized due to ionic repulsion between Fe²⁺ and DMA-detached aHA (i.e., positively charged free aHA) in the acidic environment of tumor cells. This event accelerated the release of DOX from the destabilized NPs. Our results suggest that these NPs can be promising tumor-targeting drug carriers responding to acidic endosomal pH.     

Targeting the Rac1 pathway for improved prostate cancer therapy using polymeric nanoparticles to deliver of NSC23766

Prostate cancer(PCa) is the second most commonly diagnosed cancer in men. The Rac1-GTP inhibitor NSC23766 has been shown to suppress PCa growth. However, these therapies have low tumor-targeting efficacy in vivo. Therefore, it is essential to produce a drug delivery system that specifically targets the tumor site. Herein, novel L-phenylalanine-based poly(ester amide)(Phe-PEA) polymers were synthesized and loaded with NSC23766(NSC23766@8P6 NPs), which had a small particle size(162.3 ± 6.7 nm) and...     

DNAzyme‐Loaded Metal–Organic Frameworks (MOFs) for Self‐Sufficient Gene Therapy

DNAzymes have been recognized as potent therapeutic agents for gene therapy, while their inefficient intracellular delivery and insufficient cofactor supply precludes their practical biological applications. Metal–organic frameworks (MOFs) have emerged as promising drug carriers without in‐depth consideration of their disassembled ingredients. Herein, we report a self‐sufficient MOF‐based chlorin e6‐modified DNAzyme (Ce6‐DNAzyme) therapeutic nanosystem for combined gene therapy and photodynamic therapy (PDT). The ZIF‐8 nanoparticles (NPs) could efficiently deliver the therapeutic DNAzyme without degradation into cancer cells. The pH‐responsive ZIF‐8 NPs disassemble with the concomitant release of the guest DNAzyme payloads and the host Zn²⁺ ions that serve, respectively, as messenger RNA‐targeting agent and required DNAzyme cofactors for activating gene therapy. The auxiliary photosensitizer Ce6 could produce reactive oxygen species (ROS) and provide a fluorescence signal for the imaging‐guided gene therapy/PDT.     

Biological identity of nanomaterials: Opportunities and challenges

The emergence of nanoparticles (NPs) has attracted tremendous interest of the scientific community for decades due to their unique properties and potential applications in diverse areas, including drug delivery and therapy. Many novel NPs have been synthesized and used to reduce drug toxicity, improve bio-availability, prolong circulation time, control drug release, and actively target to desired cells or tissues. However, clinical translation of NPs with the goal of treating particularly challenging diseases, such as cancer, will require a thorough understanding of how the NP properties influence their fate in biological systems, especially in vivo. Many efforts have been paid to studying the interactions and mechanisms of NPs and cells. Unless deliberately designed, the NPs in contact with biological fluids are rapidly covered by a selected group of biomolecules especially proteins to form a corona that interacts with biological systems. In this view, the recent development of NPs in drug delivery and the interactions of NPs with cells and proteins are summarized. By understanding the protein-NP interactions, some guidelines for safety design of NPs, challenges and future perspectives are discussed.     

Chitosan-Linseed mucilage polyelectrolyte complex nanoparticles of Methotrexate: In vitro cytotoxic efficacy and toxicological studies

The goal of this research was to develop, fabricate and analyze polymeric nanoparticles for the administration of methotrexate (MTX). Linseed mucilage and chitosan nanoparticles (NPs) were prepared using a slightly modified polyelectrolyte complex (PEC) method. The size, shape, and encapsulation effectiveness of the resultant nanoparticles were measured. MTX release profiles at gastrointestinal pH (1.2 and 7.4) and tumor pH (5.5) were examined to determine the targeted potential of NPs as pH-responsive nanocarriers. Zeta analysis showed that nanoparticles prepared by PEC have a size range of 192.1 nm to 246 nm, and PDI was 0.3 of the optimized formulation, which showed homogenous nature of prepared nanoparticles formulation. The findings demonstrated that NPs have a low polydispersity index and a positive zeta potential (PDI). The in-vitro release of the drug indicated a pH-dependent, sustained drug release up to 24 h. Blank LSMCSNPs had almost no in-vivo cytotoxicity for 14 days, while optimum MTX loaded NPs had strong antitumor effects on HepG2 and MCF-7 cells as measured by the MTT assay. Cell apoptosis induction was also checked and MCF-7 cells treated with MTX-LSMCSNPs had a significantly greater rate of apoptosis (21.2 %) than those treated with MTX alone (14.14 %). The findings show that LSMCSNPs could be a potential delivery mechanism for methotrexate to cancer cells in a secure, steady, and ideally controlled manner to improve therapeutic outcomes.     

Ranolazine-functionalized CuO NPs: efficient homogeneous and heterogeneous catalysts for reduction of 4-nitrophenol

In the present study copper oxide nanoparticles (CuO NPs) were synthesized using a hydrothermal method with ranolazine as a shape-directing agent. Ranolazine-functionalized CuO NPs were characterized by various analytical techniques such as scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The SEM pattern confirmed the morphology of ranolazine-functionalized CuO NPs with well-defined rice-like structures. FTIR spectroscopy confirmed the interaction between CuO NPs and ranolazine. The XRD analysis indicated that the structure of ranolazine-functionalized CuO NPs was monoclinic crystalline and the size ranged between 9 and 18 nm with an average particle size of 12 nm. The smaller size range of CuO NPs gave a large surface area that enhanced the efficiency of these catalysts employed for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the H ₂ O system. In homogeneous catalysis, results showed that 50 μL of CuO NPs was required in the presence of NaBH4 for 99% reduction of 4-NP in 240 s. On the other hand, for heterogeneous catalysis, 0.5 mg of CuO NPs was used in the presence of NaBH4 for 99% catalytic reduction of 4-NP to 4-AP in 320 s. The rate of reaction for homogeneous catalysis and heterogeneous catalysis was determined from the plots of In(Ct /C0) of 4-NP versus time (s), which showed good linearity with values of 1.3 × 10 ^-2 and 8.8 × 10 ^-3 s ^-1 . respectively. The high-quality catalytic efficiency, good reusability, nontoxic nature, and low cost are favorable properties of the synthesized CuO NPs for use as efficient catalysts for reduction of 4-AP to 4-NP in both homogeneous and heterogeneous media.     

The siRNAsome: A Cation‐Free and Versatile Nanostructure for siRNA and Drug Co‐delivery

Nanoparticles show great potential for drug delivery. However, suitable nanostructures capable of loading a range of drugs together with the co‐delivery of siRNAs, which avoid the problem of cation‐associated cytotoxicity, are lacking. Herein, we report an small interfering RNA (siRNA)‐based vesicle (siRNAsome), which consists of a hydrophilic siRNA shell, a thermal‐ and intracellular‐reduction‐sensitive hydrophobic median layer, and an empty aqueous interior that meets this need. The siRNAsome can serve as a versatile nanostructure to load drug agents with divergent chemical properties, therapeutic proteins as well as co‐delivering immobilized siRNAs without transfection agents. Importantly, the inherent thermal/reduction‐responsiveness enables controlled drug loading and release. When siRNAsomes are loaded with the hydrophilic drug doxorubicin hydrochloride and anti‐P‐glycoprotein siRNA, synergistic therapeutic activity is achieved in multidrug resistant cancer cells and a tumor model.     

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.     

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.     

A facile preparation method for nanosized MOFs as a multifunctional material for cellular imaging and drug delivery

Tb-based metal-organic framework nanoparticles (Tb-MOF NPs) with good colloidal stability and stable fluorescence properties in an aqueous solution were prepared by a simple mechanical grinding of Tb-MOF with a biocompatible polymer surfactant (F127). The characteristic fluorescence property of Tb-MOF NPs allowed us to use this nanomaterial as a cell imaging probe. Efficient cellular uptake of Tb-MOF NPs apparently via an energy-dependent endocytosis was observed by confocal laser scanning microscopy. By taking advantage of the porous nature of the Tb-MOF NPs an anticancer drug (doxorubicin) was successfully loaded and delivered to kill cancer cells to demonstrate their usage as a drug delivery vehicle. This simple grinding method afforded a nanosized, multifunctional biomaterial that was used for cell imaging and drug delivery, and it can be extended to other MOFs to widen their applications.     

Ag@TiO2 Nanoprisms with Highly Efficient Near‐Infrared Photothermal Conversion for Melanoma Therapy

Melanoma is a primary reason of death from skin cancer and associated with high lethality. Photothermal therapy (PTT) has been developed into a powerful cancer treatment technique in recent years. Here, we created a low‐cost and high‐performance PTT agent, Ag@TiO₂ NPs, which possesses a high photothermal conversion efficiency of ≈65 % and strong near‐infrared (NIR) absorption about 808 nm. Ag NPs were synthesized using a two‐step method and coated with TiO₂ to obtain Ag@TiO₂ NPs by a facile sol‐gel method. Because of the oxide, Ag@TiO₂ NPs exhibit remarkable high photothermal conversion efficiencies and biocompatibility in vivo and in vitro. Cytotoxicity and therapeutic efficiency of photothermal cytotoxicity of Ag@TiO₂ NPs were tested in B16‐F10 cells and C57BL/6J mice. Under light irradiation, the elevated temperature causes cell death in Ag NPs‐treated (100 μg mL^?1) cells in vitro (both p<0.01). In the case of subcutaneous melanoma tumor model, Ag@TiO₂ NPs (100 μg mL^?1) were injected into the tumor and irradiated with a 808 nm laser of 2 W cm^?2 for 1 minute. As a consequence, the tumor volume gradually decreased by NIR laser irradiation with only a single treatment. The results demonstrate that Ag@TiO₂ NPs are biocompatible and an attractive photothermal agent for cutaneous melanoma by local delivery.     

Highly efficient intracellular drug delivery with a negatively charged hyperbranched polysulfonamine

Efficient intracellular translocation is achieved using an easily prepared hyperbranched polysulfonamine that remains negatively charged at physiological pH. Investigations on the cellular uptake mechanism and the subcellular distribution of PSA are reported. The in vitro cytotoxicity of PSA is found to be low. Using doxorubicin as a model drug, a PSA/drug complex is prepared by electrostatic interaction with a high drug payload that exhibits a controlled release in response to pH. Efficient intracellular drug delivery, strong growth inhibition of tumor cells, and low cytotoxicity to normal cells are observed. The results suggest a possible way to utilize anionic polymers for intracellular delivery of therapeutic moieties or drugs.     

Human Serum Albumin Conjugated Nanoparticles for pH and Redox‐Responsive Delivery of a Prodrug of Cisplatin

Platinum anticancer drugs are particularly in need of controlled drug delivery because of their severe side effects. Platinum(IV) agents are designed as prodrugs to reduce the side effects of platinum(II) drugs; however, premature reduction could limit the effect as a prodrug. In this work, a highly biocompatible, pH and redox dual‐responsive delivery system is prepared by using hybrid nanoparticles of human serum albumin (HSA) and calcium phosphate (CaP) for the Pt^IV prodrug of cisplatin. This conjugate is very stable under extracellular conditions, so that it protects the platinum(IV) prodrug in HSA. Upon reaching the acidic and hypoxic environment, the platinum drug is released in its active form and is able to bind to the target DNA. The Pt–HSA/CaP hybrid inhibits the proliferation of various cancer cells more efficiently than cisplatin. Different cell cycle arrests suggest different cellular responses of the Pt^IV prodrug in the CaP nanocarrier. Interestingly, this delivery system demonstrates enhanced cytotoxicity to tumor cells, but not to normal cells.     

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.