pH-sensitive Drug Carrier Research Articles

Dual-layered pH-sensitive alginate/chitosan/kappa-carrageenan microbeads for colon-targeted release of 5-fluorouracil.

A new pH-sensitive drug carrier based on alginate (Alg), chitosan (Cs), and kappa-carrageenan (kC) marine biopolymers was developed, comprising a dual-layered polyelectrolyte complexes microbead structure. Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) were used to investigate the structures, thermal stability, and morphological changes, respectively, of the microcapsules we developed. In the intestinal environment (pH 7.4), the stability and swelling of Alg microbeads were enhanced after generation of the dual-layered polyelectrolyte complexes. The in vitro release profiles of 5-fluorouracil under simulated GI conditions were also examined. At gastric pH (1.2), the cumulative 5-FU release percentage was decreased by introduction of the additional kC layer from 14% in Alg/Cs microbeads to 7% in the dual-layered Alg/Cs/kC microbeads. Additionally, the release profiles were greatly improved under simulated intestinal and colon conditions. Finally, the microbeads were all biodegradable and showed no cytotoxicity in Chang liver cells. Our results clearly indicate that the dual-layer pH-sensitive Alg/Cs/kC microbeads could be used effectively for the targeted delivery of anticancer drugs to the colon.

Preparation and Evaluation of pH Sensitive Novel Anticancer Drug Carrier Based on Magnetic Chitosan Quartets.

Chitosan-coated magnetic nanoparticles are an appropriate drug delivery method which can improve the therapeutic properties of chemotherapy agents and also can be useful as MRI contrast agent for early cancer diagnosis. This research discovers the optimization of the possible therapeutic effects of Chitosan- citric acid- Fe3O4- CUR quartets. Chitosan as a natural polymer can use to encapsulate citric acid modified Fe3O4 nanoparticles. The successful preparation of CUR-loaded nano-carriers was confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM) and transmission electron microscopy (TEM) techniques. Moreover, the hemolysis test was used for the study of hemobiocompatibility. The loading capacity and encapsulation efficiency of CUR molecules were 11±0.09% and 49.5±0.41%, respectively. The anticancer effect of the void of CUR and CUR-loaded nano-carriers were compared by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the treated MCF-7 cell lines. It can be concluded that the use of these nanoparticles are a better and more efficient approach for the controlled and slow release of CUR in the cancer treatment.

Tracing Difference: In Vitro and in Vivo Antitumor Property Comparison of pH-Sensitive Biomimetic Phosphorylcholine Micelles with Insensitive Micelles.

Although smart polymer micelles able to respond to the tumor acid microenvironment are potential anticancer drug carriers, fruitful clinical application of these carriers is inadequate. For the purpose of finding the origin of the unsatisfactory therapeutic efficacy of pH-sensitive drug carriers with tertiary amine groups, we newly designed and synthesized poly{α-[4-(diethylamino)methyl-1,2,3-triazol]-caprolactone-co-caprolactone}-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PDCL-PMPC), a biomimetic phosphorylcholine polymer with pH-ensitive groups. PDCL-PMPC self-assembles into small and uniform micelles as its counterpart poly(caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL-PMPC) without pH-sensitive groups. The in vitro and in vivo properties of PDCL-PMPC and PCL-PMPC micelles are investigated in detail. PDCL-PMPC micelles display obvious pH sensitivity by micelle change and fast drug release at pH 5, but the insensitive micelles do not. The internalization of PDCL-PMPC micelles by tumor cells is stronger than that of PCL-PMPC micelles. However, in comparison with the insensitive micelles, the pH-sensitive micelles present much shorter blood circulation time in pharmacokinetics and demonstrate worse accumulation in the tumor site in vivo study. As a result, DOX loaded PCL-PMPC micelles demonstrate much better antitumor efficiency than pH-sensitive micelles. Furthermore, DOX loaded PCL-PMPC micelles show similar therapeutic efficacy to DOX·HCl but with considerably lower side effects.

Synthesis and characterization of PEG-functionalized graphene oxide as an effective pH-sensitive drug carrier

In the present work, PEG4000 as a hydrophilic polymer was conjugated to the surface of graphene oxide (GO) for effective drug loading and targeting release of doxorubicin. The synthesized nanohybrid was characterized with scanning electron microscope (SEM), X-ray diffraction spectroscopy (XRD) and Fourier-transformed infrared spectroscopy (FTIR). Doxorubicin as an anticancer drug was immobilized on the nanohybrid surface, and the release profile at two diverse pH besides the MTT assay was investigated. The IC50 value for the nanohybrid obtained was 0.31 μg/mL. In this work, PEG4000 as a biocompatible polymer grafted on the GO surface to increase the biodispersibility of the drug carrier in a biological environment, but it is the first report of PEG 4000-GO nanohybrid-based drug carrier.

Adsorption and encapsulation of the drug doxorubicin on covalent functionalized carbon nanotubes: A scrutinized study by using molecular dynamics simulation and quantum mechanics calculation

Adsorption of the drug doxorubicin (DOX) onto covalent functionalized carbon nanotubes (CNTs) as drug carriers was studied by employing molecular dynamics (MD) simulation. CNT was covalently functionalized by the chemical groups: amine, carboxyl and hydroxyl and the change in the electrostatic charge of CNT as a result of functionalization was investigated by quantum mechanics calculations. The drug adsorption onto the functionalized CNTs (f-CNT) was examined by analyzing the evaluated radial probability of the drug by MD simulation. Overall consideration of the results demonstrated that surface functionalization enhances the loading capacity of CNT for the drug encapsulation, also agglomeration of unprotonated drug molecules has increased encapsulation capacity. Analysis of the obtained results indicated that carboxyl and amine f-CNTs can act as a pH sensitive drug carrier where their protonation in acidic condition can decrease the electrostatic interactions of the loaded drug with the f-CNT and as a result can promote the drug release.

Preparation of novel tissue acidosis-responsive chitosan drug nanoparticles: Characterization and in vitro release properties of Ca2+ channel blocker nimodipine drug molecules

The pH-responsive intelligent drug release facility of hydrophobically modified chitosan nanoparticles (Chit NPs) (d = 5.2 ± 1.1 nm) was presented in the case of poorly water soluble Ca2+ channel blocker nimodipine (NIMO) drug molecules. The adequate pH-sensitivity, i.e. the suitable drug carrier properties of the initial hydrophilic Chit were achieved by reductive amination of Chit with hexanal (C6-) and dodecanal (C12-) aldehydes. The successful modifications of the macromolecule were evidenced via FTIR measurements: the band appearing at 1412 cm−1 (CN stretching in aliphatic amines) in the cases of the hydrophobically modified Chit samples shows that the CN bond successfully formed between the Chit and the aldehydes. Hydrophobization of the polymer unambiguously led to lower water contents with lower intermolecular interactions in the prepared hydrogel matrix: the initial hydrophilic Chit has the highest water content (78.6 wt%) and the increasing hydrophobicity of the polymer resulted in decreasing water content (C6-chit.: 74.2 wt% and C12-chit.: 47.1 wt%). Furthermore, it was established that the length of the side chain of the aldehyde influences the pH-dependent solubility properties of the Chit. Transparent homogenous polymer solution was obtained at lower pH, while at higher pH the formation of polymer (nano)particles was determined and the corresponding cut-off pH values showed decreasing tendency with increasing hydrophobic feature (pH = 7.47, 6.73 and 2.49 for initial Chit, C6-chit and C12-chit, respectively).Next the poorly water soluble NIMO drug was encapsulated with the C6-chit with adequate pH-sensitive properties. The polymer-stabilized NIMO particles with 10 wt% NIMO content resulted in stable dispersion in aqueous phase, the formation of polymer shell increased in the water solubility/dispersibility of the initial hydrophobic drug. According to the drug release experiments, we clearly confirmed that the encapsulated low crystallinity NIMO drug remained closed in the polymer NPs at normal tissue pH (pH = 7.4, PBS buffer, physiological condition) but at pH < 6.5 which is typical for seriously ischemic brain tissue, 93.6% of the available 0.14 mg/ml NIMO was released into the buffer solution under 8 h release time. According to this in vitro study, the presented pH-sensitive drug carrier system could be useful to selectively target ischemic brain regions characterized by acidosis, to achieve neuroprotection at tissue zones at risk of injury, without any undesirable side effects caused by systemic drug administration.

Potential of the Bioinspired CaCO3 Microspheres Loaded with Tetracycline in Inducing Differential Cytotoxic Effects toward Noncancerous and Cancer Cells: A Cytogenetic Toxicity Assessment Using CHO Cells in Vitro.

Calcium carbonate (CaCO3)-based materials as feasible pH-sensitive drug carriers, which can actively dissolve in an acidic microenvironment of cancer cells, are finding increasing importance. This has drawn our interest in the development of a bioinspired polypeptide- mediated method to design calcium carbonate microspheres loaded with tetracycline (CaCO3-TC) with an aim to explore its safe application in cancer therapeutics. Its therapeutic application in cancer patients essentially demands its safety information on the normal cells. Herein our study presents the in vitro genetic toxicological information on CaCO3-TC using noncancerous mammalian CHO cells in comparison to bare TC at three different concentrations (100, 200, and 300 μM) selected based on the cytotoxicity data (MTT). Assessment of various end points like chromosome aberrations, micronucleus, mitotic index and effects on cell cycle distribution after 24 h post-treatment demonstrates a significant reduction in clastogenic ( P < 0.001), aneugenic potential ( P < 0.05), and nonmitotoxic nature of CaCO3-TC than that of bare TC. Noticeably, as inferred from the FACS analysis on cancer cells, G2/M phase accumulation in breast cancer cells (MDA-MB-231), and at G1 phase in cervical cancer cells (HeLa) reveal its potential anticancer property. On the other hand, the genotoxicity studies illustrate protective effects of CaCO3-TC on noncancerous cells. While the pH-dependent dissolution property of the CaCO3 matrix encasing tetracycline results in higher toxicity on cancer cells, the near neutral pH in the case of normal cells prevents complete dissolution of CaCO3 thereby not allowing the encapsulated TC to adequately interact with the cells. Therefore, thus assembled CaCO3 spheres not only provide a way for facile encapsulation of tetracycline under mild conditions but also result in an effective matrix for differential toxicity toward normal and cancer cells justifying its clinical development as a novel target-specific drug in therapeutic applications for metastatic cancers.

Biocompatible and biodegradable zeolitic imidazolate framework/polydopamine nanocarriers for dual stimulus triggered tumor thermo-chemotherapy

Zeolitic imidazolate frameworks (ZIFs) have attracted great interest as pH-sensitive drug carrier because of high drug loading and intrinsic biodegradability. In this work, a biocompatible NIR and pH-responsive drug delivery nanoplatform based on ZIFs (PDA-PCM@ZIF-8/DOX) is synthesized for in vivo cancer therapy. The biocompatibility of ZIFs is greatly improved by polydopamine (PDA) modifying and proved by cytotoxicity and in vivo acute toxicity evaluation. The degradability is also regulated in an appropriate rate. Due to mild reaction condition of ZIFs, the synthesis and drug loading is achieved in one pot with high loading (37.86%) and encapsulation rate (78.76%). Meanwhile, PDA acts as a photothermal transfer agent to trigger thermal response switch of phase change materials for NIR controlled drug release. Under the dual stimulus of NIR and acid environment, the drug release is as high as 78%, while only 21% is released without stimulus, showing a remarkable effect of control release. In vivo anti-tumor experiments demonstrate the high tumor inhibition rate of photothermal-chemotherapy group with a significant synergistic effect. The biocompatible and biodegradable drug delivery platform based on ZIFs has shown great promise for future clinic cancer therapy.

Antifungal activity of oral (Tragacanth/acrylic acid) Amphotericin B carrier for systemic candidiasis: in vitro and in vivo study.

In an effort to increase the oral bioavailability of Amphotericin B (AmB), a pH-sensitive drug carrier composed of Tragacanth (Trag) and acrylic acid (AAc) was prepared using γ-irradiation. The swelling behavior of (Trag/AAc) hydrogels was characterized as a function of pH and ionic strength of the swelling medium. The obtained swelling indices revealed the ability of the prepared hydrogel to protect a loaded drug in stomach-simulated medium (Fickian behavior) and to release such drug in intestinal-simulated medium (non-Fickian behavior). In vitro release studies of the antifungal (AmB) were performed to evaluate the hydrogel potential as a drug carrier. The antifungal activity of the prepared oral formulation was investigated in a mouse model of systemic candidiasis. Data revealed that (Trag/AAc)-AmB has a potent antifungal efficacy as demonstrated by prolonging the survival time and reducing the tissue fungal burden, serum antibody titers, as well as inflammatory cytokines in kidney and liver tissues. Furthermore, in vivo toxicity of (Trag/AAc)-AmB was assessed via measuring kidney and liver functions, and results displayed the safety of this novel AmB formulation which was confirmed by histopathological examination. Overall, results indicated that the prepared (Trag/AAc)-AmB is an effective oral delivery system for AmB with better bioavailability and minimal toxicity and could represent a promising approach for improving the therapeutic index of the drug.

Synthesis of Au/SiO2 Nanoparticles with Highly Porous Structure as a pH-Sensitive Targeting Drug Carrier

Quercetin was loaded into disulfide-modified mesoporous silica including Au nanoparticles (Q-Au/SiO2) which had voids around Au nanoparticles. Mesoporous structures and voids in final nanoparticles could improve its loading and efficacy in drug loading. Au/SiO2 nanoparticles were decorated with disulfide di-PEG and also, were functionalized with folic acid and fluorescein isothiocyanate as targeting and fluorescence agents, respectively. Au/SiO2 nanoparticles had an average diameter of around 69 nm, which that increased to 84 nm after modification. Releasing profile of quercetin showed pH sensitive behavior and had more and faster release at acidic environment. Finally, functionalized-nanoparticles with folic acid displayed more cytotoxicity compared with nanoparticles without any modification in MCF-7 cell line.

Application of graphene quantum dots for simultaneous fluorescence imaging and tumor-targeted drug delivery

A novel drug delivery system based on arginine-glycine-aspartic acid (RGD)-conjugated graphene quantum dots (GQDs) was synthesized and utilized to load the antitumor drug doxorubicin (DOX) for targeted cancer fluorescence imaging as well as tracking and monitoring drug delivery without the need for external dyes. The inherent stable fluorescence of GQDs enables real-time monitoring of the cellular uptake of the DOX-GQDs-RGD nano-assembly and the consequent release of DOX. The release of DOX demonstrated strong pH dependence and implies hydrogen-bonding interaction between GQDs and DOX, an observation that suggests the possibility for GQDs serving as pH-sensitive drug carriers. As a nanocarrier, GQDs unlinked with DOX were nontoxic to U251 human glioma cells. Compared to free DOX, DOX-GQDs-RGD conjugates demonstrated substantial cytotoxicity to U251 glioma cells within a broad range of DOX concentrations. After applying the GQDs as drug carriers, the drug efficacy of DOX improved without concomitant DOX dosage increases. Cellular uptake results of DOX-GQDs-RGD conjugates indicate that not only DOX but also some GQDs penetrated into cell nuclei after 16h of incubation. This enhancement combined with efficient nuclear delivery improved the cytotoxicity of DOX dramatically. This type of drug delivery system based on GQDs may find widespread applications in biomedicine.

Exfoliated graphene nanosheets: pH-sensitive drug carrier and anti-cancer activity.

A straightforward and facile method for the exfoliation of graphene sheets using poly(vinylpyrrolidone) nanoparticles of an average size of 42nm was developed and their dual role as pH-sensitive drug carrier and anti-cancer agent was evaluated. The cytotoxic impact of the exfoliated nanosheets (GRP-PVP-NP) was examined on various cells (HCT-116, HeLa, SCC-9, NIH-3T3 and HEK-293cells) by a series of assays. Their cytotoxic nature was attributed to affecting the mitochondrial enzyme activity, proliferation capability, and the formation of tight junctions in cancer cells. The endocytosis was found to be internalization mechanism for the cellular uptake of nanosheets. The generation of reactive oxygen species and elicitation of caspase-3 activity which was undoubtedly associated with triggering of oxidative stress speculated to be the dominant cause of the cytotoxic pattern of nanosheets against cancer cells. Additionally, the results also showed the role of the nanosheets as a pH-sensitive drug carrier through drug loading by supramolecular interaction. The efficient release of doxorubicin was seen at low pH and in an environment with a low oxygen concentration, thus under conditions mimicking the typical tumor microenvironment. Therefore, these findings provide the first evidence for a dual function of exfoliated graphene sheets and also elucidate the cytotoxic mechanism responsible for the cancer cell death.

Effects of crystallinity and surface modification of calcium phosphate nanoparticles on the loading and release of tetracycline hydro-chloride

The influences of crystallinity and surface modification of calcium phosphate nanoparticles (nCaP) on their drug loading capacity and drug release profile were studied in the present investigation. The CaP nanoparticles with different crystallinity were prepared by precipitation method under different temperatures. CaP nanoparticles with lower crystallinity exhibited higher drug loading capacity. The samples were characterized by XRD, FT-IR, SEM, TEM and BET surface area analyzer respectively. The drug loading capacity of nCaP was evaluated to tetracycline hydro-chloride (TCH). The internalization of TCH loaded nCaP in cancer cell was observed by florescence microscope. nCaP could be stabilized and dispersed in aqueous solution by poly(acrylic acid) surface modification agent, leading to enhanced drug loading capacity. The drug release was conducted in different pH environment and the experimental data proved that nCaP were pH sensitive drug carrier, suggesting that nCaP could achieve the controlled drug release in intracellular acidic environment. Furthermore, nCaP with higher crystallinity showed lower drug release rate than that of lower crystallinity, indicating that the drug release profile could be adjusted by crystallinity of nCaP. nCaP with adjustable drug loading and release properties are promising candidate as drug carrier for disease treatment.

Preparation and evaluation of a novel anticancer drug delivery carrier for 5-Fluorouracil using synthetic bola-amphiphile based on lysine as polar heads

A novel bolaamphiphile surfactant N,N′-(dodecane-1, 12-diyl) bis (2,6-diaminohexanamide) (DADL) was designed and synthesized using l-lysine and 1,12-diaminododecane as the hydrophilic and hydrophobic part, respectively. After separation and purification, the structure of the synthetic bolaamphiphile surfactant was verified by FTIR, MS and 1H NMR. The synthetic bolaamphiphile was able to self-assemble to form vesicles. After formulation screening, vesicles loaded with 5-Fluorouracil (5-Fu) were prepared with Tween 60 and DADL by sonication and were examined by dynamic light scattering and transmission electron microscopy. Micro-FTIR was applied to investigate the conformation of the bola molecules within the vesicle membrane. The release profile of the vesicles showed a pH-sensitive and sustained release. No significant toxicity was observed in an in vitro cell viability assay. The antitumor efficacy of the 5-Fu-loaded vesicles on H22 tumor-bearing mice was remarkably high due to the EPR effects. These results show that our novel bolaamphiphile derived from lysine has excellent potential as a pH-sensitive drug carrier.

Facile fabrication of polyurethane microcapsules carriers for tracing cellular internalization and intracellular pH-triggered drug release

A tailor-made traceable pH-sensitive drug delivery system based on polyurethane (PU) microcapsules was fabricated using a facile double-emulsion method containing 3,3′-dioctadecyloxacarbocyanine perchlorate, doxorubicin (DOX) and sodium bicarbonate (NaHCO3). When PU microcapsules were immersed in acidic media, NaHCO3 could react with the H+ to quickly produce CO2 bubbles to puncture the PU shell, resulting in rapid release of DOX to promptly reach the intracellular drug therapeutic threshold to kill cancer cells in a short period. Confocal laser scanning microscopic analysis showed that these traceable pH-sensitive drug carriers can be easily internalized by BGC 823 and Hela cells, and the loaded DOX can quickly release from PU microcapsules in the endo-/lysosomes to be mainly resided in cell nuclei. This traceable pH-sensitive drug carrier can achieve on-demand controlled release profiles for visualization of cancer therapy. Thus, it is a potential candidate for anticancer drug delivery system in advanced cancer therapy.

Surface-Modification of RIPL Peptide-Conjugated Liposomes to Achieve Steric Stabilization and pH Sensitivity.

We have previously demonstrated that RIPL peptide-conjugated liposomes (RIPL-L) exhibited high hepsin (HPN) selectivity and enhanced intracellular drug delivery. In this study, surface modification of RIPL-L was performed to reduce plasma protein adsorption and off-target effects. For steric stabilization, distearoyl phosphatidylethanolamine (DSPE)-polyethylene glycol (PEG)2000 was used (5% molar ratio to total lipid) to prepare PEG-RIPL-L. Further, pH-sensitive oligopeptides [(HD)4 or (HE)4] were coupled to shield the RIPL polyarginine moiety, yielding (HD)4/PEG-RIPL-L and (HE)4/PEG-RIPL-L. All liposomal vesicles had a narrow and homogenous size distribution of approximately 140–150 nm, with zeta potentials varying from −15 to 36 mV. Increased plasma stability was observed upon quantifying the protein adsorbed onto liposomes by using a micro bicinchoninic acid assay. The (HD)4- and (HE)4-coupling capacity of PEG-RIPL-L was investigated by measuring the amount of oligopeptide involved in transient ionic complexation (TIC-oligopep) and zeta potential changes. As the molar ratio of (HD)4 and (HE)4 increased, TIC-oligopep increased and zeta potential decreased. (HE)4/PEG-RIPL-L were pH-sensitive, producing 1.6-fold greater cellular uptake of FITC-dextran by LNCaP cells at pH 6.8 than at pH 7.4. This result suggested that (HE)4/PEG-RIPL-L might provide a sterically stabilized, pH-sensitive drug carrier for HPN-specific cancer targeting.

A pH-switched mesoporous nanoreactor for synergetic therapy

Zinc oxide nanoparticles (ZnO NPs), as a new type of pH-sensitive drug carrier, have received much attention. ZnO NPs are stable at physiological pH, but can dissolve quickly in the acidic tumor environment (pH < 6) to generate cytotoxic zinc ions and reactive oxygen species (ROS). However, the protein corona usually causes the non-specific degradation of ZnO NPs, which has limited their application considerably. Herein, a new type of pH-sensitive nanoreactor (ZnO-DOX@F-mSiO2-FA), aimed at reducing the non-specific degradation of ZnO NPs, is presented. In the acidic tumor environment (pH < 6), it can release cytotoxic zinc ions, ROS, and anticancer drugs to kill cancer cells effectively. In addition, the fluorescence emitted from fluorescein isothiocyanate (FITC)-labeled mesoporous silica (F-mSiO2) and doxorubicin (DOX) can be used to monitor the release behavior of the anticancer drug. This report provides a new method to avoid the non-specific degradation of ZnO NPs, resulting in synergetic therapy by taking advantage of ZnO NPs-induced oxidative stress and targeted drug release.

Effects of intermolecular interactions on the stability of carbon nanotube-gold nanoparticle conjugates in solution.

This work deals with the role of intermolecular interactions in the stability of a carbon nanotube (CNT) capped by functionalized gold nanoparticles (AuNPs). The importance of such a system is due to its potential application as a pH-controlled drug carrier. Our preliminary experimental studies showed that fabrication of such a nanobottle/nanocontainer is feasible and it is possible to encapsulate the anticancer drug cisplatin inside the inner space of a CNT and seal its ends by functionalized AuNPs. The expected behavior, that is, detachment of AuNPs at acidic pH and the release of cisplatin, was, however, not observed. On the other hand, our theoretical studies of chemically identical system led to the conclusion that the release of cisplatin at acidic pH should be observed. Therefore, in this work, a deeper theoretical analysis of various factors that could be responsible for the disagreement between experimental and theoretical results were performed. The study found that the major factor is a large dispersion interaction component acting between CNT and AuNP in solution in the case of the experimental system. This factor can be controlled to some extent by tuning the system size or the ratio between AuNP diameter and CNT diameter. Thus, such kind of a pH-sensitive drug carrier is still of great interest, but its structural parameters need to be properly adjusted.

Simultaneous delivery of Paclitaxel and Bcl-2 siRNA via pH-Sensitive liposomal nanocarrier for the synergistic treatment of melanoma.

pH-sensitive drug carriers that are sensitive to the acidic (pH = ~6.5) microenvironments of tumor tissues have been primarily used as effective drug/gene/siRNA/microRNA carriers for releasing their payloads to tumor cells/tissues. Resistance to various drugs has become a big hurdle in systemic chemotherapy in cancer. Therefore delivery of chemotherapeutic agents and siRNA’s targeting anti apoptotic genes possess advantages to overcome the efflux pump mediated and anti apoptosis-related drug resistance. Here, we report the development of nanocarrier system prepared from kojic acid backbone-based cationic amphiphile containing endosomal pH-sensitive imidazole ring. This pH-sensitive liposomal nanocarrier effectively delivers anti-cancer drug (Paclitaxel; PTX) and siRNA (Bcl-2), and significantly inhibits cell proliferation and reduces tumor growth. Tumor inhibition response attributes to the synergistic effect of PTX potency and MDR reversing ability of Bcl-2 siRNA in the tumor supporting that kojic acid based liposomal pH-sensitive nanocarrier as efficient vehicle for systemic co-delivery of drugs and siRNA.

Highly fluorescent and morphology-controllable graphene quantum dots-chitosan hybrid xerogels for in vivo imaging and pH-sensitive drug carrier

Highly fluorescent graphene quantum dots (GQDs)-chitosan (CS) hybrid xerogels (GQDs-CS) were facilely synthesized, and the morphology of GQDs-CS was controllable by varying the content of GQDs in the xerogel. The GQDs-CS exhibited a porous and three-dimensional (3D) network structure when the content of GQDs reached 43% (wt%) in the xerogel, which was beneficial for drug loading and sustained release. The as-prepared GQDs-CS could also be applied for in vivo imaging since it showed strong blue, green and red luminescence under excitation of varying wavelengths. Moreover, the pH-induced protonation/deprotonation of the –NH2 groups on CS chains can result in a pH-dependent drug delivery behavior of the GQDs-CS hybrid xerogel.