Stimuli-responsive Drug Delivery Systems Research Articles

Fluorescent multi-responsive cross-linked P(N-isopropylacrylamide)-based nanocomposites for cisplatin delivery

Magnetic, pH and temperature-sensitive, poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites with fluorescent properties were synthesized by free radical copolymerization-cross linking of NIPAM, N,N-dimethylaminoethyl methacrylate (DMAEMA) and 4-acrylamidofluorescein (AFA). The model anti-cancer drug, cisplatin (CDDP), was loaded into the resulted nanogel. For the production of CDDP-loaded nanocomposite, Fe3O4 magnetic nanoparticles (MNPs) and CDDP were loaded into the nanogel. Field-emission scanning electron microscopy (FE-SEM) indicated that the size of nanogel and CDDP-loaded nanocomposite were about 90 and 160 nm, respectively. The encapsulation efficiency of CCDP was found up to 65%. The loaded CCDP showed sustained thermal and pH-responsive drug release. A high level of drug release was observed under the conditions of low pH and high temperature. The lower critical solution temperature (LCST) of synthesized nanogel was about 40 °C. CDDP-loaded nanocomposite showed a volume phase transition from 282 to 128 nm at its LCST. Accordingly, in this study, the synthesized nanocomposite can be employed as a stimuli-responsive anti-cancer drug delivery system and the pH and temperature of solution have the potential to monitor the drug release.

PH-Sensitive Nanoscale Polymers: Highly Efficient Systems for DOX Delivery in Cancer Treatment

Recently, many stimuli-responsive drug delivery systems based on biodegradable and biocompatible polymers have been introduced for controlled release of anticancer drug Doxorubicin. The main role of polymers in these systems is to provide high loading of Doxorubicin and then control the release of the drug in low pH-media. Polymeric micelles and nanoparticles such as magnetic particles, silica and graphene oxide covered with smart polymers include two main categories of Dox-controlled release systems. Herein, we review aforementioned systems which have been used for Doxorubicin release through different response of the system in terms of pH including: swelling or expansion of the polymeric chains, pH-sensitive bond cleavage and loss of electrostatic interactions between the drug and system. The mechanism of drug loading, drug release, advantages and disadvantages of each system are fully discussed.

A facile one-step method for preparation of Fe3O4/CS/INH nanoparticles as a targeted drug delivery for tuberculosis

In this paper, Fe3O4/chitosan/isoniazid magnetic nanoparticles (Fe3O4/CS/INH-MNPs) were prepared as an environmental stimuli-responsive drug-delivery system by automated in situ click technology, in which Fe3O4 magnetic nanoparticles, chitosan and isoniazid were simultaneously in situ crystallized by one-step method. The Fe3O4 magnetic nanoparticles and tripolyphosphate act as stable crosslinkers to produce numerous intermolecular crosslinkages for the mobility of the chitosan chains. Characterization results indicated that the multifunctional drug delivery system with optimized size, excellent loading capacity, well magnetic properties, nontoxicity and pH triggered drug release property is expected to be applied in tuberculosis treatment with excellent magnetic sensitivity and sustained release.

English

Marine environment with rich biodiversity offer unlimited choice for novel biopolymers. Sulfated polysaccharides isolated from marine algae and bacteria constitute an important group in the marine-derived biomolecules and biopolymers. They possess unique structural features which can be exploited to their fullest potential in the development of new therapeutic molecules, design of nanocarriers and stimuli-responsive drug delivery systems, development of anti-aging and moisturizing creams and as molecular probes in diagnosis of cancers and cardiovascular diseases. The aim of the present review is to highlight the sources, characteristics and applications of sulfated polysaccharides and exopolysaccharides isolated from marine algae, cyanobacteria, extremophilic and halophilic bacteria. Detailed description of physicochemical properties and versatile applications of ulvan, fucoidan, galactofucan sulfate, laminarin, mauran, cyanobacterial exopolysaccharides and other lesser known exopolysaccharides of marine bacterial origin has been provided. In a nutshell, it can be concluded that sustainable exploitation of the renewable, diverse library of these unique and novel sulfated polysaccharides will unravel newer possibilities in future and will enrich the existing arsenal of biopolymers. Key words: Exopolysaccharide, marine biopolymer, molecular probe, nanocarriers, stimuli-responsive drug delivery systems, sulfated polysaccharide.

Anaerobe-Inspired Anticancer Nanovesicles.

Anaerobic bacteria, such as Clostridium and Salmonella, can selectively invade and colonize in tumor hypoxic regions (THRs) and deliver therapeutic products to destroy cancer cells. Herein, we present an anaerobe nanovesicle mimic that can not only be activated in THRs but also induce hypoxia in tumors by themselves. Moreover, inspired by the oxygen metabolism of anaerobes, we construct a light-induced hypoxia-responsive modality to promote dissociation of vehicles and activation of bioreductive prodrugs simultaneously. In vitro and in vivo experiments indicate that this anaerobe-inspired nanovesicle can efficiently induce apoptotic cell death and significantly inhibit tumor growth. Our work provides a new strategy for engineering stimuli-responsive drug delivery systems in a bioinspired and synergistic fashion.

PH-Responsive Aerobic Nanoparticles for Effective Photodynamic Therapy.

Rationale: Photodynamic therapy (PDT), an O2-dependent treatment for inhibition of cancer proliferation, suffers from the low therapeutic effect in clinical application due to the hypoxic microenvironment in tumor cells.Methods: To overcome this obstacle, a stimuli-responsive drug delivery system with O2 self-sufficiency for effective PDT was developed. In this study, pH-responsive aerobic nanoparticles were prepared by the electrostatic interaction between the O2-evolving protein Catalase and Chitosan. Subsequently, the photosensitizer Chlorin e6 (Ce6) was encapsulated in the nanoparticles.Results: The nanoparticles exhibited high stability in aqueous medium and efficient cellular uptake by tumor cells facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. In acidic environment, irradiation caused disassembly of the nanoparticles resulting in the quick release of Catalase and the photosensitizer with continuous formation of cytotoxic singlet oxygen (1O2) greatly enhancing the PDT efficacy in hypoxic tumor tissues both in vitro and in vivo biological studies.Conclusion: Due to the unique O2 self-sufficiency, the nanoparticles, upon irradiation, exhibited higher anticancer activity than free Ce6 both in vitro and in vivo. Our work has identified a new pH-triggered strategy to overcome hypoxia for effective PDT against cancer cells.

Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment.

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs), quantum dots (QDs) and carbon nanotubes (CNTs). The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules) and extrinsic (temperature, light irradiation, magnetic field and ultrasound) ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.

Biomimetic synthesis of sericin and silica hybrid colloidosomes for stimuli-responsive anti-cancer drug delivery systems

Colloidosomes are becoming popular due to their significant flexibility with respect to microcapsule functionality. This study reports a facile approach for synthesizing silica colloidosomes by using sericin microcapsule as the matrix in an environment-friendly method. The silica colloid arrangement on the sericin microcapsules are orchestrated by altering the reaction parameters. Doxorubicin (DOX), used as a hydrophilic anti-cancer drug model, is encapsulated into the colloidosomes in a mild aqueous solution and becomes stimuli-responsive to different external environments, including pH values, protease, and ionic strength are also observed. Colloidosomes with sub-monolayers, close-packed monolayers, and close-packed multi-layered SiO2 colloid shells can be fabricated under the optimized reaction conditions. A flexible DOX release from colloidosomes can be obtained via modulating the SiO2 colloid layer arrangement and thickness. The close-packed and multi-layered SiO2 colloid shells can best protect the colloidosomes and delay the rapid cargo release. MG-63 cells are killed when doxorubicin is released from the microcapsules due to degradation in the microenvironment of cancer cells. The drug release period is prolonged as SiO2 shell thickness and integrity increase. This work suggests that the hybrid colloidosomes can be effective in a bioactive molecule delivery system.

Carbon-Dot-Coated Alginate Beads as a Smart Stimuli-Responsive Drug Delivery System.

In this work, we report a smart stimuli-responsive drug delivery system (DDS) that can release drug depending upon the amount of pathogen (MRSA) present in the target. A greater amount of MRSA in the system will lead to more release of drug and vice versa. Carbon-dot-coated novel alginate beads (CA-CD) exhibiting superior stability was successfully used as smart drug delivery vehicle. Garlic extract (GE), which contains allicin, was taken as model drug system to demonstrate the phenomena. It was observed that GE loading was 19 and 78% with CA and CA-CD, respectively. CA-CD-GE shows pH-dependent controlled drug release, which results in increased therapeutic efficiency. CA-CD-GE is not only stimuli responsive but also a controlled drug release system as it releases drug according to the pathogen concentration (MRSA). All the three factors viz. drug release, MRSA concentration and pH of the medium are interdependent as when the cell divides, it produces secondary metabolites that lead to the decrease in pH of the medium. The drop in the pH value triggers drug release from the beads. And the effect of the drug is reflected by the MRSA cell death. Hence, we demonstrate a smart stimuli responsive DDS. However, such DDS will be useful in cases where increased amount of pathogen in the system will lead to reduction in pH.

Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system

Context: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.Objective: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.Materials and methods: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.Results: LSH tablets exhibited dynamic swelling–deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.Discussion: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.Conclusions: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

A Multifunctional Nanocrystalline CaF2:Tm,Yb@mSiO2 System for Dual-Triggered and Optically Monitored Doxorubicin Delivery.

Daunting challenges in investigating the controlled release of drugs in complicated intracellular microenvironments demand the development of stimuli-responsive drug delivery systems. Here, a nanoparticle system, CaF2:Tm,Yb@mSiO2, made of a mesoporous silica (mSiO2) nanosphere with CaF2:Tm,Yb upconversion nanoparticles (UCNPs) is developed, filling its mesopores and with its surface-modified with polyacrylic acid for binding the anticancer drug molecules (doxorubicin, DOX). The unique design of CaF2:Tm,Yb@mSiO2 enables us to trigger the drug release by two mechanisms. One is the pH-triggered mechanism, where drug molecules are preferentially released from the nanoparticles at acidic conditions unique for the intracellular environment of cancer cells compared to normal cells. Another is the 808 nm near infrared (NIR)-triggered mechanism, where 808 nm NIR induces the heating of the nanoparticles to weaken the electrostatic interaction between drug molecules and nanoparticles. In addition, luminescence resonance energy transfer occurs from the UCNPs (the energy donor) to the DOX drug (the energy acceptor) in the presence of 980 nm NIR irradiation, allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs. This study demonstrates a new multifunctional nanosystem for dual-triggered and optically monitored drug delivery, which will facilitate the rational design of personalized cancer therapy.

Poly(acrylic acid) conjugated hollow mesoporous carbon as a dual-stimuli triggered drug delivery system for chemo-photothermal synergistic therapy

In this work, we described the development of the redox and pH dual stimuli-responsive drug delivery system and combination of the chemotherapy and photothermal therapy for cancer treatment. The poly(acrylic acid) (PAA) was conjugated on the outlets of hollow mesoporous carbon (HMC) via disulfide bonds. PAA was used as a capping to block drug within the mesopores of HMC for its lots of favorable advantages, such as good biocompatibility, appropriate molecular weight to block the mesopores of HMC, extension of the blood circulation, and the improvement of the dispersity of the nano-carriers in physiological environment. The DOX loaded DOX/HMC-SS-PAA had a high drug loading amount up to 51.9%. The in vitro drug release results illustrated that DOX/HMC-SS-PAA showed redox and pH dual-responsive drug release, and the release rate could be further improved by the near infrared (NIR) irradiation. Cell viability experiment indicated that DOX/HMC-SS-PAA had a synergistic therapeutic effect by combination of chemotherapy and photothermal therapy. This work suggested that HMC-SS-PAA exhibited dual-responsive drug release property and could be used as a NIR-adsorbing drug delivery system for chemo-photothermal synergistic therapy.

Unimolecular Micelles of Amphiphilic Cyclodextrin-Core Star-Like Copolymers with Covalent pH-Responsive Linkage of Anticancer Prodrugs.

Multifunctional stable and stimuli-responsive drug delivery systems are important for efficient cancer treatment due to their advantages such as enhanced cancer-targeting efficiency, improved pharmacokinetics, minimized drug leaching, and reduced undesirable side effects. Here we report a robust and pH-responsive anticancer drug delivery system based on unimolecular micelles of star-like amphiphilic copolymers. The polymers (denoted as CPOFs) were facilely synthesized via one-step atom transfer radical polymerization of functionalizable benzoaldehyde and hydrophilic poly[(oligo ethylene glycol) methyl ether methacrylate] as comonomers from the core of heptakis [2,3,6-tri-o-(2-bromo-2-methyl propionyl]-β-cyclodextrin as the initiator. Doxorubicin (DOX) as an anticancer drug was covalently linked to the benzoaldehyde groups of CPOFs through pH-sensitive Schiff-base bonds. The DOX-conjugated polymers, denoted as CPOF-DOX, formed robust unimolecular micelles with an average diameter of 18 nm in aqueous media. More importantly, these unimolecular micelles showed higher drug loading capacity and more controllable drug release characteristics, compared to our previous unimolecular micelles of β-cyclodextrin-poly(lactic acid)-b-poly[(oligo ethylene glycol) methyl ether methacrylates] that physically encapsulated DOX via hydrophobic interaction. Moreover, the CPOF-DOX unimolecular micelles could be internalized by human cervical cancer HeLa cells in a stepwise way and showed less cytotoxicity compared to carrier-free DOX. We foresee that CPOF-DOX would provide a promising robust and controllable anticancer drug delivery system for future animal study and clinical trials for cancer treatment.

Sustained, Controlled and Stimuli-Responsive Drug Release Systems Based on Nanoporous Anodic Alumina with Layer-by-Layer Polyelectrolyte.

Controlled drug delivery systems are an encouraging solution to some drug disadvantages such as reduced solubility, deprived biodistribution, tissue damage, fast breakdown of the drug, cytotoxicity, or side effects. Self-ordered nanoporous anodic alumina is an auspicious material for drug delivery due to its biocompatibility, stability, and controllable pore geometry. Its use in drug delivery applications has been explored in several fields, including therapeutic devices for bone and dental tissue engineering, coronary stent implants, and carriers for transplanted cells. In this work, we have created and analyzed a stimuli-responsive drug delivery system based on layer-by-layer pH-responsive polyelectrolyte and nanoporous anodic alumina. The results demonstrate that it is possible to control the drug release using a polyelectrolyte multilayer coating that will act as a gate.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1585-4) contains supplementary material, which is available to authorized users.

Controlled assemblies of stimuli-responsive mesoporous silica drug delivery systems for controlled release of drugs

There has been an ever increasing interest in developing stimuli-responsive mesoporous silica drug delivery systems to improve therapeutic efficacy and minimize the adverse effects of drugs. This paper reports the works of our research group on valved and gated mesoporous silica drug delivery systems. Biocompatible mesoporous silica nanoparticles (MSNs), as drug carriers, were modified with active group-terminated silanes via self-assembly followed by diverse functionalization, a variety of macrocyclic hosts, proteins, DNA, and quantum dots were bound to the MSN surfaces to develop nanovalves and nanogates, through multiple noncovalent interactions, dynamic covalent bonds, and even strong covalent bonds, for the encapsulation of drugs within MSN pores, thus smart valved and gated MSN drug delivery systems were constructed. Under the stimuli of pH, redox, competitive binding, enzymes, and near infrared lights, controlled release of the encapsulated drugs was realized, because of the destruction of multiple noncovalent interactions, the cleavage of dynamic covalent bonds, and the disassociation of gatekeeping scaffolds. The carboxylate-substituted pillar [6] arene (CPA [6] )-valved dimethylbenzimidazolium or bipyridinium-functionalized MSN drug delivery systems were constructed for acidic pH, competitive binding, and metal chelating-responsive controlled release. The γ -CD-gated MSN delivery system functionalized with disulfide-linked carbamoylphenylboronic acid moieties and amines via dual dynamic covalent bonds with dual drug loading was constructed for simultaneous and cascade release of two drugs. It is a smart strategy to take advantage of the specific structures and properties of cyclodextrins (CDs) for use in the MSN drug delivery systems not only as gatekeepers but also as drug carriers. The γ -CD-gated MSN delivery system provided a smart platform for combination drug therapy, in addition to resistance to serum and normal blood glucose levels. The concanavalin A (Con A)-gated mannose-functionalized MSN drug delivery system via multivalent carbohydrate - protein interactions was constructed for the controlled release of drugs either by acidic pH or by competitive binding of glucose at high concentrations. The long and flexible spacers linked with the mannose ligands played an important role in adjusting the local spatial arrangement of the ligands to favor multivalent protein binding, as did the surface density of the ligands. The MSN drug delivery systems functionalized with N -(3-trimethoxysilylpropyl)ethylenediamine triacetate ligands, in the presence of metal ions with and without myoglobin containing surface-accessible histidine residues, were constructed for pH-responsive controlled release. Both the metal-latching ligands and the metal-chelating proteins played a synergetic role in gating MSNs for high-loading drug delivery and stimuli-responsive controlled release. The DNA-gated MSN drug delivery system functionalized with disulfide-linked acridinamine intercalators was constructed for multi-responsive controlled release under different stimuli, including disulfide reducing agents, elevated temperature, and deoxyribonuclease I. The DNA-gated MSN drug delivery system integrated multiple responses and AND logic gate operations into a single smart nanodevice not only for codelivery of drugs and DNA/genes but also for cascade release of two drugs in combination of dual stimuli. The DNA-gated gold nanorod-embedded MSN delivery system functionalized with titanium(IV)-chelating phosphonates with dual drug loading was constructed for simultaneous and cascade release of two drugs. Coordination chemistry is the first strategy for DNA cappings through multivalent chelating interactions in drug delivery systems not only as gatekeepers but also as drug carriers. The two drugs were simultaneously released upon triggering of endonuclease degradation or photothermal dehybridization and were successively released upon first triggering of basic pH and subsequent triggering of photothermal heating. The combination of NIR light-based thermotherapy and triggered chemotherapy (thermo-chemotherapy) could maximize therapeutic efficacy. In addition, the ZnO quantum dot (QD)-gated hollow mesoporous silica drug delivery system was constructed for pH and redox- responsive controlled release, and the ZnO QD-gated mesoporous carbon nanoparticle (MCN) drug delivery system was for pH-responsive controlled release. These constructed stimuli-responsive MSN drug delivery systems have promising applications in targeted tumor therapy.

Inhibition of the cancer-associated TASK 3 channels by magnetically induced thermal release of Tetrandrine from a polymeric drug carrier

Two-pore domain (K2P) potassium channels have recently attracted growing interest in the field of cancer research. These channels play an important role in cancer biology specifically for cancer progression, including proliferation, migration, and apoptosis, which makes them an attractive target for novel cancer therapies. Here, we examined the effect of Tetrandrine (Tet), a natural compound known as a channel modulator, which is associated with anticancer activities, as potential drug in this regard. Xenopus oocyte with overexpression of K2P 9.1 (TASK 3) channels has been chosen as model system for this purpose. In order to release Tet and trigger the channels we developed a polymeric magnetic delivery system: Tetrandrine-Magnetite co-loaded poly (lactic-co-glycolic) acid particles. The embedded iron oxide magnetite (Fe3O4) nanoparticles (NPs) allow to inductively heat the particles by applying a high frequency alternating magnetic field, and thus trigger the release of the co-encapsulated Tet. As a proof of concept the nanoparticulate drug delivery system was heated by raising the suspension's temperature proving the temperature dependent release behaviour. Both heating approaches were then successfully applied for measuring the TASK 3 channels current in response to the released drug. It was found that the released Tet amount is sufficient to inhibit the TASK 3 channels in a dose dependent manner. Thus, such a stimulus responsive drug delivery system holds great promise as a novel approach for the treatment of various cancer types such as for the interaction with the two-pore domain potassium channels K2P 9.1.

Near-Infrared Light-Triggered Switchable Nanoparticles for Targeted Chemo/Photothermal Cancer Therapy.

Accumulation of nanoparticles in solid tumors depends on their extravasation, but their efficacy is often compromised by intrinsic physiological heterogeneity in tumors. The conventional solutions to circumvent this problem are size control of nanoparticles or increasing the vascular permeability. The aim of this study is to investigate the combination effect of size variation of stimuli-responsive nanoparticles and improved vascular permeability triggered by near-infrared (NIR) light irradiation. Doxorubicin (DOX), a clinically proven drug for bladder cancer, was encapsulated in the nanocomposites with high loading content up to 45%. We show that NIR light-responsive size-switchable nanocarriers could considerably enhance the tumor-targeting of DOX in bladder tumor-bearing mice. Moreover, a combination of NIR-induced hyperthermia and DOX-mediated chemotherapy resulted in remarkable inhibition of tumor growth in mice. Histological results suggest that the change in morphology of tumor microvasculature may account for enhanced extravasation and accumulation of the nanodrugs upon NIR irradiation. Together, these data suggest that external stimuli-responsive drug delivery system offers a safe and effective means of targeted chemo/photothermal therapy.

Fe3O4@ZnS@Glycine nanoparticle as a novel microwave stimulus controlled drug release system

The stimuli-responsive controlled drug delivery system is highly desirable for an efficient cancer treatment approach. Herein, we have successfully developed a novel multifunctional microwave stimulus controlled anticancer drug release system based on magnetic Fe3O4@ZnS@Glycine nanoparticles. Fe3O4 core has a high magnetization saturation value for drug targeting under foreign magnetic fields. ZnS shells can efficiently convert microwave energy into thermal energy for microwave-triggered drug release. The glycine-modified layer of nanoparticles provides active group (–NH2) for the loading of drug molecules by hydrogen bond. The in vitro studies have clearly demonstrated the feasibility and advantage of the novel nanocarriers for remote-controlled drug release systems. We combined the advantages of ZnS nanoparticles with those of Fe3O4 and glycine to create a new drug delivery system, which is capable of carrying drug molecules and triggered release of the drug by microwave treatment.

Advances in Peptide Functionalization on Mesoporous Silica Nanoparticles for Controlled Drug Release.

During the last decade, using versatile, promising, and fascinating mesoporous silica nanoparticles (MSNs) as site-specific and stimuli-responsive drug delivery systems (DDSs) has received concentrated research interest. As one of the most attractive surface modification units, peptides have inherent bioactivity, biodegradability and biocompatibility. Recent progresses in the utilization of versatile peptides for surface functionalization of MSNs to achieve cell-specific targeting, fluorescence imaging, and intracellular diagnosis and treatment of tumors are summarized in this review. The various functional peptides decorated on the MSNs are introduced and classified into three types, including targeting peptides, stimuli-responsive peptides and multifunctional chimeric peptides. The limitations and challenges of peptide modified MSNs and their potential applications are further discussed.

Peptide-Decorated Gold Nanoparticles as Functional Nano-Capping Agent of Mesoporous Silica Container for Targeting Drug Delivery.

A stimuli-responsive drug delivery system (DDS) with bioactive surface is constructed by end-capping mesoporous silica nanoparticles (MSNs) with functional peptide-coated gold nanoparticles (GNPs). MSNs are first functionalized with acid-labile α-amide-β-carboxyl groups to carry negative charges, and then capped with positively charged GNPs that are decorated with oligo-lysine-containing peptide. The resulting hybrid delivery system exhibits endo/lysosomal pH triggered drug release, and the incorporation of RGD peptide facilitates targeting delivery to αvβ3 integrin overexpressing cancer cells. The system can serve as a platform for preparing diversified multifunctional nanocomposites using various functional inorganic nanoparticles and bioactive peptides.