DOX-loaded Nanocarriers Research Articles

Thermo and pH-responsive nanocarriers based on mesocellular silica foam and poly(N-vinylcaprolactam-co-methacrylic acid): Synthesis, characterization, and in vitro cytotoxicity assay

Smart hybrid nanocarriers were prepared by grafting poly(N-vinylcaprolactam-co-methacrylic acid) (poly(NVCL-co-MAA)) onto mesocellular silica foams (MCF silica) to evaluate them as controlled delivery systems of doxorubicin (DOX). The development of these nanocarriers began with the synthesis of MCF silica with interconnected porous structures and an average pore diameter of 27 nm. Then, free radical polymerization was used to graft the smart copolymer, and some parameters such as comonomer concentration and reaction time were studied. The DOX was loaded by immersion in an aqueous drug solution, while the in vitro release was investigated at different pHs (7.4, 5.8) and temperatures (25, 37 °C). In addition, the cytotoxicity of nanocarriers was investigated in vitro using the direct contact method with human breast cancer cells (SKBR3). In general, hybrid nanocarriers with copolymer graft percentages ranging from 30 to 60 % were obtained. On the other hand, at higher grafting of poly(NVCL-co-MAA) onto MCF silica, higher drug loading (up to 6.41 × 10−2 mg DOX/mg HN) was observed. Furthermore, in vitro DOX release results suggested that the nanocarriers released up to 52 % at 37 °C and a pH of 5.8. Finally, the in vitro cytotoxicity assay revealed that the DOX-loaded hybrid nanocarriers were cytotoxic to SKBR3 cells, indicating a controlled administration of DOX from the nanocarriers compared to free DOX. These results suggest that nanocarriers could have great potential for use as controlled delivery systems of anticancer drugs.

Biotinylated Theranostic Amphiphilic Polyurethane for Targeted Drug Delivery.

In the area of drug delivery aided by stimuli-responsive polymers, the biodegradability of nanocarriers is one of the major challenges that needs to be addressed with the utmost sincerity. Herein, a hydrogen sulfide (H2S) responsive hydrophobic dansyl-based trigger molecule is custom designed and successfully incorporated into the water-soluble polyurethane backbone, which is made of esterase enzyme susceptible urethane bonds. The amphiphilic polyurethanes, PUx (x = 2 and 3) with a biotin chain end, formed self-assembled nanoaggregates. A hemolysis and cytotoxicity profile of doxorubicin (DOX)-loaded biotinylated PU3 nanocarriers revealed that it is nonhemolytic and has excellent selectivity toward HeLa cells (biotin receptor-positive cell lines) causing ∼60% cell death while maintaining almost 100% cell viability for HEK 293T cells (biotin receptor-negative cell lines). Furthermore, better cellular internalization of DOX-loaded fluorescent nanocarriers in HeLa cells than in HEK 293T cells confirmed receptor-mediated endocytosis. Thus, this work ensures that the synthesized polymers serve as biodegradable nanocarriers for anticancer therapeutics.

DOX-loaded mesoporous hydroxyapatite modified by hyaluronic acid can achieve efficient targeted therapy for lung cancer

It is a novel therapeutic strategy to suppress tumour growth and metastasis by regulating the interaction between bioactivity ions and the biological process of tumour cells. This study synthesised a mesoporous hydroxyapatite (MHAP)-based nanocarrier for targeted delivery of the anti-cancer drug doxorubicin (DOX). To further strengthen the targeting of DOX-loaded nanocarrier to tumour, HA that could specifically identify receptor on the surface of tumours was functionally modified. The drug release properties curve showed that the MHAP-HA@DOX complex showed pH-sensitive and sustained release properties. Also, the MHAP-HA@DOX complex represented high toxicity against lung cancer A549 cells. Besides, it displayed a significant inhibitory effect on tumour growth rate in tumour-bearing mice, while no evident toxicity for mice was observed. This nano-material is hoped to be an effective and novel nano-drug for lung cancer.

Fabrication of pH and thermal dual-responsive hyperbranched copolymer grafted magnetic graphene oxide via surface-initiated RAFT-SCVP for controlled release of DOX

Herein, a novel stimuli-responsive magnetic graphene oxide/hyperbranched copolymer nanocomposites (GO@Fe3O4 @HBC) was prepared via mixing surface-initiated RAFT and self-condensing vinyl polymerization technique. In the first step, chain transfer monomer (CTM) was synthesized by the esterification reaction between 2-(dodecylthiocarbonothioylthio)− 2-methylpropionic acid (DDMAT) and 2-Hydroxyethyl methacrylate (HEMA). Besides, graphene oxide nanosheets were decorated with Fe3O4 nanoparticles. The surface of magnetic graphene oxide nanosheets was modified with 3-amino propyl (trimethoxysilyl) (APTS) and then the DDMAT was anchored to the surface of their nanosheets via amidification reaction. At last, smart hyperbranched poly (NIPAM-co-AA) was effectively grafted to the surface of magnetic graphene oxide using the SI-RAFT-SCVP technique. The chemical and physical structure of the synthesized GO@Fe3O4 @HBC were investigated by FT-IR, H NMR, GPC, TGA, DLS, CHN, VSM, UV-Vis, SEM, EDAX, and TEM. The synthesized GO@Fe3O4 @HBC was used as a nanocarrier. The drug delivery efficacy of this nanocarrier was investigated in terms of in vitro doxorubicin (DOX) release and MTT assay against HeLa cells, which confirms both acidic pH and thermo-sensitive behavior. The MTT assay also revealed that the nanocarrier without DOX was biocompatible having cell viability greater than 90% for HeLa cells. DOX-loaded nanocarrier showed high cytotoxic effect on HeLa Cells.

Tuning the surface chemistry of 2D MXenes for optimizing the micellization of bio-targeted carriers

Using nanocarriers to deliver drugs to cancer cells is an effective way to treat cancer. However, this method faces several challenges, including the instability of nanocarriers, and the appropriate method for the synthesis of nanocarriers. In this regard, in this work, the effect of the two-dimensional MXene in increasing the stability of riboflavin-targeted PLGA-PEG nanocarriers for delivering doxorubicin (Dox) has been investigated using molecular dynamics simulation. In this study, the role of surface chemistry engineering of MXene in optimizing Dox-loaded micelles has been studied. On the other hand, the effect of the microfluidic method on the synthesis of nanocarriers has been investigated. According to the obtained results, the use of MXene has outstandingly increased the stability of Dox-loaded nanocarriers. MXene increases the attraction energy between micelles from −600 Kj/mol to −1700 Kj/mol. But the use of hydrophilic functional groups in the MXene has reduced the stability of nanocarriers. The molecular analysis approves the greater stability of nanocarriers synthesized by the microfluidic method in comparison to non-microfluidic method. Finally, this could lead to the widespread use of microfluidic synthesis as well as MXene in the synthesis of nanocarriers.

Synthesis, characterization, and evaluation of pH-sensitive doxorubicin-loaded functionalized graphene oxide in osteosarcoma cells.

Doxorubicin (DOX) is one of the most common drugs in cancer treatment. However, its partial solubility along with the high incidence of side effects remains a challenge to tackle. To address these issues, we designed a formulation based on graphene oxide (GO) and used it as an anticancer drug delivery system. The physical and chemical properties of the formulation were studied using FTIR, SEM, EDX, Mapping, and XRD. Release studies in the in vitro condition were used to evaluate the pH sensitivity of drug release from nanocarriers. Other in vitro studies, including uptake assay, MTT, and apoptosis assay were carried out on the osteosarcoma cell line. in vitro release studies confirmed that the synthesized formulation provides a better payload release profile in acidic conditions, which is usually the case in the tumor site. On the OS cell line, the cytotoxicity of the DOX-loaded nanocarrier (IC50=0.293 μg/mL) and early apoptosis rate (33.80 % ) were higher in comparison to free DOX (IC50=0.472 μg/mL, and early apoptosis rate= 8.31 % ) after 48 hours. In summary, our results suggest a DOX-loaded graphene oxide carrier as a potential platform for targeting cancer cells.

Hyper-branched multifunctional carbon nanotubes carrier for targeted liver cancer therapy

The systemic toxicity of anticancer drugs regularly restricts the use of conventional chemotherapy to treat cancer. In this study, the limitations overcome by profitably fabricating a multifunctional nanocarrier system to carry the anticancer drug into the specific location of the cancer cells. The polyethylene glycol (PEG) was functionalized in the carboxylated multiwalled carbon nanotubes (MWCNT-COOH) through an esterification reaction (MWCNT-PEG). The targeting ligand of folic acid (FA) was covalently bonded with hyperbranched poly-L-lysine (HBPLL) using adipic acid (AA) as a cross-linking agent. Doxorubicin (DOX), an anticancer drug, was effectively loaded on MWCNT-PEG-AA-HBPLL-FA carrier loading, and in-vitro drug release was investigated by UV–Vis spectrophotometer. The chemical functionalization, morphological properties, crystalline nature, surface charge, and thermal stability of the synthesized materials were studied by FT-IR, FE-SEM, HR-TEM, DLS, and TGA techniques. In-vitro cytotoxicity and anticancer properties of DOX-loaded nanocarrier were studied in human liver cancer (HepG2) cells and human embryonic kidney (HEK293) cells. The activities of caspases (caspase −3, −8 & −9) were analyzed using luminometry. The intrinsic apoptosis pathway proteins (Bcl-2 & BAX) were determined by western blot and RT-PCR analysis. The synthesized DOX-loaded nanocarriers exhibited increased cytotoxicity and apoptosis in liver HepG2 cells. The results suggest that the DOX-loaded nanocarrier possesses strong anticancer properties and could be an applicable and potential drug carrier for liver cancer chemotherapy.

One Pot Silica Nanoparticle Modification and Doxorubicin Encapsulation as pH-Responsive Nanocarriers, Applying PEG/Lysine Aqueous Two Phase System

Providing an efficient system for drug delivery and chemotherapy has always been an important issue. Here, we have presented an aqueous two-phase system (ATPS) based on polyethylene glycol and lysine, which can partition doxorubicin (DOX) as an anticancer drug successfully. Addition of SiO2 nanoparticles to ATPS increased the partitioning of doxorubicin (DOX) as an anticancer drug from 47.92 in the absence of nanoparticles to 92.33 due to interactions between drug and nanoparticles. This novel biocompatible ATPS simultaneously modified the surface of SiO2 nanoparticles and loaded doxorubicin (DOX) on the modified SiO2 using hydrogen bonding interactions in one pot. Modification of the surface of SiO2 provides an opportunity for achieving a stimulus-sensitive drug delivery system. The formation of nanoformulation and its characteristics were investigated using microscopy, spectroscopy, and thermal analysis. Drug release study demonstrated that DOX is loaded on nanoformulations efficiently with an encapsulation efficiency of 63.84% and shows lower release in physiological environment compared to the unmodified nanoparticles. While in acidic conditions of pH 5.5, a significant increase was observed in the release profile. MTT assay on MCF-7 cancer cells confirmed that the nanoformulations were non-toxic and DOX-loaded nanocarrier showed anticancer behavior. These results indicate that the prepared nanoformulations are promising nanocarriers for controlled drug release purposes.

Bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers for efficient targeted anticancer drug delivery.

Functionalization of nanocarriers has been considered the most promising way of ensuring an accurate and targeted drug delivery system. This study reports the synthesis of bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers with an excellent ability to deliver doxorubicin (DOX), an anticancer drug, into the intercellular matrix. Here, the presence of amine and carboxylate groups enables aspartic acid (AA) to be used as an efficient anchoring molecule for the conjugation of folic acid (FA) (EDC–NHS coupling) and DOX (electrostatic interaction). Based on the results, surface functionalization showed little effect on the physicochemical properties of the nanoparticles but significantly influenced both the loading and release efficiency of DOX. This is primarily caused by the steric hindrance effect due to large and bulky FA molecules. Furthermore, in vitro MTT assay of B16–F1 cell lines revealed that FA conjugation was responsible for a significant increase in the cytotoxicity of DOX-loaded nanocarriers, which was also found to be proportional to AA concentration. This high cytotoxicity resulted from an efficient cellular uptake induced by the over-expressed folate receptors and fast pH triggered DOX release inside the target cell. Here, the lowest IC50 value of DOX-loaded nanocarriers was achieved at 2.814 ± 0.449 μg mL−1. Besides, further investigation also showed that the drug-loaded nanocarriers exhibited less or no toxicity against normal cells.

Drug Release Kinetics of DOX-Loaded Graphene-Based Nanocarriers for Ovarian and Breast Cancer Therapeutics

Cancer remains one of the leading causes of death worldwide despite extensive efforts at developing curative treatments. Chemotherapy, one of the most common forms of treatment, lacks specificity and can induce collateral damages to healthy surrounding tissues/cells and elicit off-target toxic side effects. The carbon-based nanomaterial graphene, can load aromatic drugs with high efficiency, has good biocompatibility, and can be easily functionalised with targeting ligands, antibodies, and biomolecules to increase the accuracy of targeting specific areas; graphene has therefore been explored as a nanocarrier for classical chemotherapy drugs. In this work, seventeen publications that report the release of doxorubicin (DOX) from 2D graphene-based nanohybrids (graphene oxide and reduced graphene oxide) for the treatment of breast and ovarian cancers have been identified based on a range of inclusion and exclusion criteria. To aid in the clinical translation of proof-of-concept studies, this work identifies the pre-clinical experimental protocols and analyses the release kinetics of these publications. Fifteen of the papers utilised a change in pH as the stimulus for drug release, and two utilised either near infrared (NIR) or ultrasound as the stimulus. The extracted drug release data from these publications were fit to four known kinetic models. It was found that the majority of these data best fit the Weibull kinetic model. The agreement between the kinetic data in previously published literature provides a predictable estimation of DOX release from graphene-based nanocarriers. This study demonstrates the potential conjugation of graphene and DOX in drug delivery applications, and this knowledge can help improve to the design and formulation of future graphene-based nanocarriers. In addition, the use of further experimental testing and the standardisation of experimental protocols will be beneficial for future work. The incorporation of computational modelling prior to pre-clinical testing will also aid in the development of controlled and sustained DOX release systems that offer efficient and efficacious results.

Synthesis of core-shell structure based on silica nanoparticles and methacrylic acid via RAFT method: An efficient pH-sensitive hydrogel for prolonging doxorubicin release

In recent years, much attention has been received on stimuli-responsive nanocarriers in nanomedicine. In this work, a pH-responsive core-shell system based on silica nanoparticles (SNPs) as core and methacrylic acid hydrogels as shell were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Methacrylic acid hydrogel through bulk and RAFT polymerization was developed as a model to compare with core-shell hydrogel. The synthesized nanocarriers were characterized by TGA, FT-IR, SEM, TEM, and DLS techniques. To investigate the synthesized core-shell nanoparticles as anticancer nanocarriers, Doxorubicin (DOX) was used as a model drug. In-vitro drug release manner at physiological barriers (pH 7.4) and cancer cell conditions (pH 4.8) illustrates a pH-controlled release for the nanocarriers over 15 days. The study of drug release kinetics reveals that the release mechanism of the carriers followed by the Gompertz model. In addition, the DOX-loaded nanocarriers have notable cytotoxicity against human breast MCF-7 cells with 0.7866 μM IC50 for core-shell nanocarrier. The obtained results showed that the prepared pH-responsive core-shell hydrogel has a high potential to be employed as a sustained pH-sensitive drug release system.

Direct surface modification of mesoporous silica nanoparticles by DBD plasma as a green approach to prepare dual-responsive drug delivery system

This paper deals with uniformly surface modification of mesoporous silica nanoparticles by applying dielectric barrier discharge (DBD) plasma as an energy-efficient and green approach. First, the mesoporous silica nanoparticles were synthesized from rice husk (RMSN-D) as an economic and biocompatible natural source. The surface modification stage by DBD plasma was performed in two methods: i) Direct mode and ii) Direct hybrid mode. The structure and physicochemical properties of the nanoparticles were characterized by XRD, FT-IR, Fe-SEM/EDS, TEM, EDS, BET, and HNMR techniques. Doxorubicin (Dox) was exploited as a model drug, and in-vitro Dox release was investigated. The biocompatibility of nanocarriers was accepted by MTT test on HFF-2 cell line as a normal modal cell. For the advanced cellular study, apoptosis of the MCF-7 cell line treated with Dox-loaded nanocarriers was investigated by flow cytometric analysis and morphological study by fluorescent microscopy. The results showed that Dox-loaded RMSN-D modified by direct hybrid mode induced a high level of apoptosis in the MCF-7 cells.

Preparation and in-vitro evaluation of mesoporous biogenic silica nanoparticles obtained from rice and wheat husk as a biocompatible carrier for anti-cancer drug delivery

In this study, mesoporous silica nanocarriers were synthesized from natural sources such as rice and wheat husk for drug delivery application. First, the biogenic silica in cereals husk was extracted by acid leaching and then converted to sodium silicate as a silica precursor. Mesoporous silica nanoparticles were then synthesized by adding sodium silicate to the template mixture by continuous and discrete modes during the sol-gel process. The effects of natural sources type and precursor addition method on nanocarriers‘ morphological and physicochemical properties were investigated by XRD, FT-IR, BET and SEM analysis. Our results showed rice husk-based spherical nanocarriers were more crystalline with slit-shaped pores, while wheat husk-based nanocarriers had been composed of spherical nanoparticles with narrow cylindrical pores. The results also showed that by adding the precursor discretely, their hydrophilicity, particle size and pore size increased compared with the continuous mode, probably due to the high initial concentration of the precursor in the reaction mixture. Doxorubicin (Dox), as a model anticancer drug was loaded into the nanocarriers, and the drug release behavior was studied at two different pH values (7.4 and 5.4). In general, the accumulated released drug at pH 5.4 was approximately twice as much as pH 7.4 due to the higher solubility of doxorubicin at acidic environment. Also, the accumulated released drug at pH 5.4 for nanocarriers which had been synthesized by discrete mode, was higher than continuous mode, due to the larger pore diameter of them. The biocompatibility and cytotoxicity of nanocarriers and Dox-loaded nanocarriers were also investigated on the HFF-2 and MCF-7 cell lines, respectively. Moreover, apoptosis, as the mechanism of cell death, was evaluated by morphological study of the MCF-7 cells. Within acceptable toxicity limits and apoptosis induction, the Dox-loaded nanocarriers, especially discrete mode synthesized nanocarriers, exhibited high-efficiency anticancer effect on the MCF-7 cell line.

Doxorubicin Stability and Retention on PEGylated Graphene Oxide Nanocarriers Adjacent to Human Serum Albumin.

Drug stability and retention on nanocarriers is essential for maximizing the drug targeting and therapeutic efficiency. PEGylation of graphene oxide (GO) as a drug nanocarrier is widely known to prolong its circulation time in the body, thereby increasing the probability of drug delivery system interactions with the proteins in the blood stream. Herein, molecular dynamics (MD) simulations were performed to investigate the interactions between doxorubicin (DOX)-loaded GO and PEGylated GO (PEGGO) nanocarriers with human serum albumin (HSA), a prevalent human blood protein and among the first to be adsorbed on the DOX-loaded nanocarriers. The results indicate that drug stability and retention on PEGGO nanocarriers are far more superior to the GO nanocarriers (control) when in contact with HSA. It is also demonstrated in this work that the PEGGO nanocarriers retain the DOX molecules irrespective of the HSA Sudlow site I and II orientations, thereby revealing their robustness in DOX loading.

Doxorubicin Imprinted Photoluminescent Polymer as a pH-Responsive Nanocarrier.

In this work, an innovative doxorubicin (DOX) imprinted photoluminescent polymer via the precipitation free-radical polymerization strategy was developed based on graphene quantum dots as a pH-responsive nanocarrier. The prepared materials were characterized by Fourier transform infrared, scanning electron microscopy, photoluminescence, and dynamic light scattering techniques. Binding kinetics of DOX established specific recognition binding sites in the photoluminescent nanoscale molecularly imprinted polymer (PLMIP) structure. In vitro drug release behaviors exhibited a pH-controlled release in a sustained manner for the prepared photoluminescent nanocarriers. Due to the presence of pseudopeptide skeletons in the nanocarrier and a positively charged structure, the cytotoxicity study indicated that a DOX-loaded nanocarrier against human lung adenocarcinoma A549 cell lines has notable cytotoxicity. According to the obtained results, the prepared pH-responsive PLMIP has the potential to be employed as an anticancer and biodetection platform.

Luminescent silicon-based nanocarrier for drug delivery in colorectal cancer cells

Nanocarriers sensitive to exogenous or endogenous stimuli emerged as an attractive alternative to target drug delivery, with inorganic silica mesoporous nanoparticles (MNs) playing a core role in the development of a new generation of non-toxic and tuneable nanocarriers. A sensitive nanovector (NANO1) comprising luminescent silicon quantum dots (SiQDs) and functionalized with MNs was synthesised and loaded with doxorubicin (DOX). NANO1 nanoparticles have a size of 74 ± 10 nm and DOX loading percentages of ca. 43%. As a control sample, a similar nanocarrier (NANO2), without SiQDs, was also synthesised and loaded with DOX. Release profile studies, in PBS, revealed the strong NANO1@DOX pH-dependant behaviour, with a pH 5.0 favouring the release of DOX to percentages of ca. 70%. Cytotoxicity assessments of both free and DOX-loaded nanocarriers were evaluated in human cell lines of colon, revealing both free drug and drug-loaded nanoparticles to be concentration-dependent.

Hyaluronidase-Functionalized Silica Nanocarrier for Enhanced Chemo-Immunotherapy through Inducing Immunogenic Cell Death.

The chemo-immunotherapy has become a highly prospective method for cancer treatment, and it has been known that chemotherapeutic drugs [e.g., doxorubicin (DOX)] could trigger antitumor immune responses. Yet, insufficient tumor penetrability and weak immunogenic cell death (ICD) severely limits the therapeutic effect of chemo-immunotherapy against cancer. Herein, we report the design of DOX-loaded silica nanocarriers (DOX@HMSPHs) with hyaluronidase functionalization, which could increase the permeability of drug and induce enhanced ICD effect through the degradation of hyaluronic acid (HA) in the extracellular matrix (ECM). Interestingly, the controlled release of DOX from DOX@HMSPHs in the acidic microenvironment induced ICD of tumor cells to release tumor antigens and damage-associated molecular patterns, promoting the antigen-presentation of dendritic cells (DCs) and the activation of specific tumor immunity. Moreover, HMSPHs could be used as an immune adjuvant to promote maturation of DCs, thereby promoting the activation of tumor infiltrating cytotoxic T lymphocytes. This strategy presents a concept to improve the efficacy of chemo-immunotherapy through degradation of HA in the ECM.

Chimeric poly(N-isopropylacrylamide)-b-poly(3,4-dihydroxy-L-phenylalanine) nanocarriers for temperature/pH dual-stimuli-responsive theranostic application

A series of poly(N-isopropylacrylamide)60-block-poly(3,4-dihydroxy-L-phenylalanine)n (p(NIPAM)60-b-p(DOPA)n) (n = 30, 50, 75, 100) copolymers have been prepared by combining reversible addition fragmentation chain transfer polymerization with ring opening polymerization of N-carboxyanhydride α-amino acid using N-heterocyclic carbene as an organocatalyst. The copolymers form spherical nanoparticles with an average diameter of ~100 nm by self-assembly. Doxorubicin (Dox) is encapsulated in the spherical nanocarriers with a drug loading efficiency of 44.2%. The iron(III) ions are coordinated to the copolymer matrix via catechol moieties in p(DOPA) units, resulting in temperature/pH dual-stimuli-responsive nanocarriers. The microstructures and Dox loading procedure can be predicted using a dissipative particle dynamics simulation. Cellular uptake and theranostic anticancer activity studies reveal that the nanocarriers release encapsulated Dox preferentially in cancer cells in response to morphological changes induced by variations in temperature and pH. Both cell internalization and cytotoxicity in A2780 ovarian cancer cells and in vivo biodistribution studies demonstrate that the Dox-loaded nanocarriers fabricated by p(NIPAM)-b-p(DOPA) copolymers can be a promising candidate for cancer therapy.

Tetraphenylsilane-Cored Star-Shaped Polymer Micelles with pH/Redox Dual Response and Active Targeting Function for Drug-Controlled Release.

This paper presents the design and synthesis of star-shaped copolymers with two poly[2-(diethylamino)ethyl methacrylate] and poly(ethylene glycol) blocks linked via a disulfide bond and each end of the four arms capped by folic acid (FA), from which the prepared nanodrug carriers simultaneously possess pH/redox dual response and active targeting functions. The polymer micelles exhibit excellent stability as reflected by their low critical micelle concentration values of 1.03-2.51 mg/L. The doxorubicin (DOX)-loaded polymer micelles are in the range of 108 to 143 nm, and the DOX-loading capacities are found to be up to 32.3%. The sensitive pH and redox responses are demonstrated by examining the drug release behaviors under the varied acidic condition from pH 7.4 to 5.0 and the glutathione concentrations from 0 to 10 mM, respectively. Moreover, the observation of confocal laser scanning microscopy confirms that the functionalization of arm ends by FA indeed enhances the internalization of DOX-loaded micelle particles in HeLa cells. As a result, the DOX-loaded nanocarriers can deliver therapeutic drugs to target HeLa cells, and the viability of HeLa cells (10.1%) approaches the value of the pristine DOX (9.98%), showing promising application as drug delivery nanocarriers for safe and highly efficient cancer therapy.

Gold-capped mesoporous silica nanoparticles as an excellent enzyme-responsive nanocarrier for controlled doxorubicin delivery

Mesoporous silica nanoparticles (MSNs) have ideal characteristics as next generation of controlled drug delivery systems. In this study, a MSN-based nanocarrier was fabricated and gold nanoparticle (GNP)-biotin conjugates were successfully grafted onto the pore outlets of the prepared MSN. This bioconjugate served as a capping agent with a peptide-cleavable linker sensitive to matrix metalloproteinases (MMPs), which are overexpressed extracellular proteolytic enzymes in cancerous tissue. The prepared nanocarriers were fully characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infra-red spectroscopy (FTIR), dynamic light scattering (DLS) and thermo gravimetric analysis (TGA). In vitro release studies showed efficient capping of MSNs with gold gate and controlled release of Doxorubicin (DOX) in the presence of matrix metalloproteinase-2 (MMP-2) and acidic pH values. High DOX-loading capacity (21%) and encapsulation efficiency (95.5%) were achieved using fluorescence technique. DOX-loaded nanocarriers showed high cytocompatibility and could efficiently induce cell death and apoptosis in the MMP-2 overexpressed cell lines. Moreover, Haemolysis, platelet activation and inflammatory responses assessment approved excellent hemocompatibility and minimal side effects by encapsulation of DOX in MSNs carrier.