pH-responsive Drug Delivery System Research Articles

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system.

Most cancer chemotherapy regimens rely on the use of two or more chemotherapeutic agents. However, achieving the best possible dosing of the individual drugs can be challenging due to differences in metabolism, uptake, and clearance among other factors. Here we describe a supramolecular strategy for achieving drug delivery in which the loading ratio of two active components is easily defined. Specifically, we report the formation of aggregates comprised of self-assembled amphiphiles between carboxylatopillar[6]arene (CP6A) and an oxaliplatin (OX)-type Pt(iv) prodrug (PtC10). The association constant (K a) for the underlying host-guest interaction at pH 7.4 ((1.16 ± 0.03) × 104 M-1) is an order of magnitude higher than at pH 5.0 ((1.73 ± 0.15) × 103 M-1). A second chemotherapeutic, doxorubicin (DOX), may be encapsulated in the resulting vesicles (PtC10⊂CP6A) to give a supramolecular combination chemotherapeutic system DOX@PtC10⊂CP6A. Drug release studies served to confirm that PtC10 and DOX are released in acidic environments. Support for a synergistic antiproliferative effect relative to PtC10 + DOX came from cellular studies of DOX@PtC10⊂CP6A using the human liver hepatocellular carcinoma (HepG-2) cell line. In vivo studies revealed that DOX@PtC10⊂CP6A is not only able to retard tumor growth efficiently but also reduce drug-related toxic side effects in BALB/c nude mice bearing HepG-2 subcutaneous tumor xenografts. These favorable findings are attributed to the formation of a ternary complex that benefits from an enhanced permeability and retention (EPR) effect in vivo while allowing for the pH-based release of PtC10 and DOX at the tumor site.

Fabrication and Antitumor Mechanism of a Nanoparticle Drug Delivery System: Graphene Oxide/Chitosan Oligosaccharide/γ‐Polyglutamic Acid Composites for Anticancer Drug Delivery

AbstractThis study focused on the design of a novel pH responsive nanoparticle drug delivery system (NDDS) with high biocompatibility and water solubility. The designed system was used for doxorubicin (DOX) delivery at tumor sites in a controlled manner. These innovative nanoparticles are soluble in physiological solutions besides water. In this study, pretreated γ‐polyglutamic acid (γ‐PGA) aqueous solutions were loaded into composites of graphene oxide (GO) covalently linked with chitosan oligosaccharide (CO) to fabricate GO‐CO‐γ‐PGA via amidation. The characterizations of the synthesized samples were carried out by using fourier transform infrared spectrometer (FTIR), X‐ray photoelectron spectrometer (XPS), ultraviolet– visible spectrophotometer (UV‐Vis), transmission electron microscopy (TEM), atomic force microscope (AFM) and zeta potential. Furthermore, drug loading and release behaviors from GO‐CO‐γ‐PGA were studied. The DOX loading in the constructed nanocarriers (GO‐CO‐γ‐PGA‐DOX) resulted in controlled and sustained release. The results of cell experiments revealed that the synthesized composites, which were easily transferred into cells, showed low toxicity and exhibited excellent antitumor effect due to its good connection with DOX. In addition, the composite nanoparticles caused the cell cycle arrest of Hela cells at the G2/M phase. Western blot results indicated that GO‐CO‐γ‐PGA‐DOX downregulated the expression of Bcl‐2 protein but upregulated Bax protein expression, which triggered the release of cytochrome C (Cytc). This condition further activated caspase‐3, cleaved the substrate of poly ADP‐ribose polymerase (PARP), and caused cell apoptosis. These results demonstrated that GO‐CO‐γ‐PGA‐DOX induces apoptosis via the intrinsic mitochondrial apoptotic pathway. Hence GO‐CO‐γ‐PGA composites have promising application in the field of biomedicine.

Liposomes with pH responsive ‘on and off’ switches for targeted and intracellular delivery of antibiotics

pH responsive drug delivery systems are one of the new strategies to address the spread of bacterial resistance to currently used antibiotics. The aim of this study was to formulate liposomes with ‘On’ and ‘Off’’ pH responsive switches for infection site targeting. The vancomycin (VCM) loaded liposomes had sizes below 100 nm, at pH 7.4. The QL-liposomes had a negative zeta potential at pH 7.4 that switched to a positive charge at acidic pH. VCM release from the liposome was quicker at pH 6 than pH 7.4. The OA-QL-liposome showed 4-fold lower MIC at pH 7.4 and 8- and 16-fold lower at pH 6.0 against both MSSA and MRSA compared to the bare drug. OA-QL liposome had a 1266.67- and 704.33-fold reduction in the intracellular infection for TPH-1 macrophage and HEK293 cells respectively. In vivo studies showed that the amount of MRSA recovered from mice treated with formulations was 189.67 and 6.33-fold lower than the untreated and bare VCM treated mice respectively. MD simulation of the QL lipid with the phosphatidylcholine membrane (POPC) showed spontaneous binding of the lipid to the bilayer membrane both electrostatic and Van der Waals interactions contributed to the binding. These studies demonstrated that the ‘On’ and ‘Off’ pH responsive liposomes enhanced the activity targeted and intracellular delivery VCM.

"Two in one": Simultaneous functionalization and DOX loading for fabrication of nanodiamond-based pH responsive drug delivery system.

Nanodiamond (ND) has been widely studied as a new type of carbon nanomaterials that is expected to be used as a promising candidate in various fields especially in the field of biomedicine. However, its poor water dispersibility and insufficient controlled release limit its practical applications. In this paper, ND-based composites with pH-responsive hydrazone bonds were successfully prepared by a simple chemical reaction between ester groups and hydrazine hydrate, in which ester groups were conjugated on the surface of ND via thiol-ene click reaction. On the other hand, CHO-PEG and doxorubicin hydrochloride (DOX) were linked on the carriers through formation of hydrazone bonds, resulting in improving water dispersibility and high drug loading capacity. The structure, thermal stability, surface morphology and particle size of ND carriers were characterized by different equipment. Results demonstrated that we have successfully prepared these functionalized ND. The release rate of DOX in acidic environment was significantly greater than that in normal physiological environment. More importantly, cell viability and optical imaging results showed that ND-based composites possess good biocompatibility, therapeutic effect, and could successfully transport DOX to HepG2 cells. Considering the above results, we believe that our new ND carriers will become promising candidates for intracellular controlled drug delivery and cancer treatment.

PEGylated MoS2 quantum dots for traceable and pH-responsive chemotherapeutic drug delivery

Since low pH value is widely observed in most of solid tumors, pH-responsive drug delivery system (DDS) can provide a general strategy for tumor-targeting therapy. In this work, a traceable and pH-responsive DDS (MoS2-PEG-DOX) based on MoS2 quantum dots (MoS2 QDs) is successfully developed by covalently grafting MoS2 QDs with diamine-terminated oligomeric polyethylene glycol (PEG) and then loading with a fluorescent antineoplastic anthracycline drug, doxorubicin (DOX). The functionalization of MoS2 QDs with PEG imparts the nanocomposite with strong blue photoluminescence, low cytotoxicity, and excellent physiological stability. The MoS2-PEG-DOX nano-assembly can be effectively taken up by U251 cells, and an accelerated DOX release is then triggered by intracellular acid condition, which in turn diminishing unwanted side effects derived by the incorporation of DOX into healthy cells. Meanwhile, the cellular uptake of the MoS2-PEG-DOX nano-assembly, consequent DOX release and the localization of nanocarrier can be real-time monitored due to the inherent stable fluorescence of MoS2-PEG and DOX. These findings demonstrate that MoS2-PEG-DOX will be promising for high treatment efficacy with minimal side effects in future therapy.

PH-Responsive Lipid-Dendrimer Hybrid Nanoparticles: An Approach To Target and Eliminate Intracellular Pathogens.

pH-responsive drug delivery systems are yielding opportunities to directly deliver antibiotics to the site of infection. Therefore, this study aimed to develop and evaluate novel pH-responsive lipid-dendrimer hybrid nanoparticles (LDH-NPs) for the delivery of vancomycin (VCM) to the site of infection, by intracellular bacterial pathogens. The LDH-NPs were formulated using the emulsification solvent evaporation method and were characterized by various in vitro and molecular dynamic (MD) simulation techniques. LDH-NPs were 124.4 ± 2.01 nm in size, with a zeta-potential of -7.15 ± 2.98 mV and drug entrapment efficiency of 82.70 ± 4.09%, which exhibited pH-responsive behavior by shifting the surface charge from negative at physiological pH to positive in acidic pHs, with a size increase from 124.4 ± 2.01 to 173.9 ± 13.38 nm, and 252.7 ± 3.98 nm at pHs of 7.4, 6.0, and 4.5, respectively. Results indicated that the in vitro drug release of VCM from LDH-NPs occurred faster at pH 6.0 than at pH 7.4. The antibacterial activity of LDH-NPs against methicillin-resistance Staphylococcus aureus (MRSA) showed 8-fold lower MICs at pH 6.0 and 7.4, compared to treatment with VCM only. A bacterial cell viability study showed LDH-NPs had an 84.19% killing of MRSA, compared to VCM (49.26%) at the same MIC, further confirming its efficacy. Cell uptake studies showed that LDH-NPs intracellularly accumulated in HEK 293 cells, confirming significant clearance (p < 0.0001) of intracellular bacteria. MD simulation showed that interaction between the dendrimer and oleylamine was predominantly governed by van der Waals (VdW) interactions; whereas the interaction between the dendrimer and VCM was governed by both VdW and electrostatic interactions. Therefore, this study concludes that the pH-responsive release of VCM enhanced antibacterial efficacy against MRSA and intracellular delivery of an antibiotic. Thus, LDH-NPs is a promising nanocarrier system for antibiotics with the potential to improve the treatment outcomes of bacterial infections in patients with antibiotic resistant strains.

Double-Hydrophilic Block Copolymers Based on Functional Poly(ε-caprolactone)s for pH-Dependent Controlled Drug Delivery.

The use of double-hydrophilic block copolymers (DHBCs) in biomedical applications is limited by their lack of degradability. This additional functionality has been obtained in the past through multistep chemical strategies associated with low yields. In this work, a series of DHBCs composed of a bioeliminable poly(ethylene glycol) (PEG) block and hydrolyzable functional poly(ε-caprolactone) (PCL) blocks bearing carboxylic (PEG-b-PCL(COOH)), amino (PEG-b-PCL(NH2)), or hydroxyl side groups (PEG-b-PCL(OH)) is synthesized in only three steps. DHBCs with 50% substitution degree with respect to the CL units are obtained for all functional groups. The pH-dependent self-assembly behavior of the DHBCs is studied showing critical micelle concentration (CMC) variations by a factor of 2 upon pH changes and micellar mean diameter variations of 20-30%. The potential of these partly degradable DHBCs as drug-loaded polyion complex micelles is further exemplified with the PEG-b-PCL(COOH) series that is associated with the positively charged anticancer drug doxorubicin (DOX). Encapsulation efficiencies, drug loadings, pH-controlled release, and cytotoxicity of the DOX-loaded micelles toward cancer cells are demonstrated. This set of data confirms the interest of the proposed straightforward chemical strategy to generate fully bioeliminable and partly degradable DHBCs with potential as pH-responsive drug-delivery systems.

Hyaluronic acid-targeted and pH-responsive drug delivery system based on metal-organic frameworks for efficient antitumor therapy

Drug delivery systems (DDSs) have emerged to help delivering the required cargo into the region of the tumor, achieving the objectives of extenuating the potential damage to the body and improving the therapeutic effectiveness. Here, we developed a one-pot process for encapsulating the unstable and hydrophobic d-α-Tocopherol succinate (α-TOS) in zeolitic imidazolate framework-8 (ZIF-8) compounds (defined as α-TOS@ZIF-8) and subsequently coated with a hyaluronic acid (HA) shell to form the HA/α-TOS@ZIF-8 nanoplatform. Of particular note was when the concentration of α-TOS is l mg/mL, the loading rate was high up to 43.03 wt%. The study verified that HA shell, which could act as a smart “switch” and tumor-targeted “guider”, had the capacity for extending blood circulation, enhancing the tumor-specific accumulation of DDS via CD44-mediated pathway. HA shell could be disintegrated by hyaluronidase (HAase) in the tumor microenvironment (TME) and the wrapped α-TOS@ZIF-8 exposed, thus leading to the decomposition of ZIF-8 in tumor acidic microenvironment to release the loaded α-TOS. Therefore, the HA/α-TOS@ZIF-8 nanoplatform has been achieved as a tumor-specific and on-demand drug delivery system, which improved the treatment efficiency.

Temperature and pH-responsive nano-hydrogel drug delivery system based on lysine-modified poly (vinylcaprolactam).

BackgroundSmart materials capable of responding to external stimuli are noteworthy candidates in designing drug delivery systems. In many of the recent research, temperature and pH have been recognized as the main stimulating factors in designing systems for anti-cancer drugs delivery systems.PurposeIn this study, thermo and pH-responsive character of a nano-carrier drug delivery platform based on lysine modified poly (vinylcaprolactam) hydrogel conjugated with doxorubicin was assessed.MethodsPoly (vinylcaprolactam) cross-linked with poly (ethyleneglycol) diacrylate was prepared via RAFT polymerization, and the prepared structure was linked with lysine through ring-opening. The anti-cancer drug doxorubicin, was linked to lysine moiety of the prepared structure via Schiff-base reaction. The prepared platform was characterized by 1HNMR and FT-IR, while molecular weight characterization was performed by size exclusion chromatography. The temperature-responsive activity was evaluated using differential scanning calorimetry and dynamic light scattering. In vitro release pattern in simulated physiologic pH at 37°C was compared with acidic pH attributed to tumor site and elevated temperature. The anticancer efficiency of the drug-conjugated structure was evaluated in breast cancer cell line MCF-7 in 24 and 48 h, and cell uptake assay was performed on the same cell line.ConclusionAccording to the results, well-structure defined smart pH and temperature responsive nano-hydrogel was prepared. The enhanced release rates are observed at acidic pH and elevated temperature. We have concluded that the doxorubicin-conjugated nanoparticle results in higher cellular uptakes and more cytotoxicity.

Ecofriendly one pot fabrication of methyl gallate@ZIF-L nanoscale hybrid as pH responsive drug delivery system for lung cancer therapy

Abstract Zeolitic imidazole frame work, a special class of porous crystalline material with tunable pore size has emerged as a promising candidate for biomedical applications. The present work enlightens the fabrication of methyl gallate encapsulated ZIF-L (MG@ZIF-L) by utilizing red seaweed Gracilaria debilis and evaluating its anticancer potential against lung cancer cell lines A549. The material structure and physicochemical behaviors were systemically investigated using several spectroscopic techniques. Results showed that MG@ZIF-L possessed high loading efficiency, biocompatibility and fast drug release in tumor microenvironment, revealing that ZIF-L would act as a promising drug delivery system for cancer therapy. In vitro anticancer experiments illustrated that MG@ZIF-L exhibited high cytotoxic effects against A549 cells. Fluorescent microscopic analysis confirmed that MG@ZIF-L enhanced intracellular reactive oxygen species, causing mitochondrial dysfunction, releasing cytochrome C, the key factor for apoptosis. Moreover, in vitro and in vivo toxicity studies using PBMC and zebra fish embryo as model systems confirmed the nontoxic nature of MG@ZIF-L. Overall, the present work highlights the possibility of developing MG@ZIF-L nanocomposite as a suitable candidate for lung cancer therapy.

Dual-responsive nanoparticles based on chitosan for enhanced breast cancer therapy

In this study, we report a novel pH and temperature responsive paclitaxel-loaded drug delivery system based on chitosan and di(ethylene glycol) methyl ether methacrylate. This was functionalized with hyaluronic acid to permit active targeting of CD44-overexpressing human breast cancer cells. The resultant HA-CS-g-PDEGMA-PTX nanoparticles (NPs) have small and uniform sizes (˜170 nm), a high drug loading (13.6 ± 1.3%) and high encapsulation efficiency (76.2 ± 8.5%). Cell viability and confocal microscopy experiments demonstrated that the NPs could effectively target and kill MDA-MB-231 human breast cancer cells, but were much less toxic to healthy human umbilical vein endothelial cells. In vivo biodistribution studies in mice showed that the NPs accumulated in the tumor site, while free drug was distributed more widely and rapidly cleared from the body. Histopathological studies revealed that the NPs led to enhanced apoptosis in the tumor site, which resulted in reduced tumor growth. The NPs prepared in this work have great potential for the treatment of breast cancers, and further offer a platform with which to target other cancers.

PH-Responsive i-motif Conjugated Hyaluronic Acid/Polyethylenimine Complexes for Drug Delivery Systems.

i-motif is cytosine (C)-rich oligonucleotide (ODN) which shows pH-responsive structure change in acidic condition. Therefore, it has been utilized for the trigger of intercalated drug release, responding to environmental pH change. In this study, 2.76 molecules of i-motif binding ODNs (IBOs) were conjugated to each hyaluronic acid (HA) via amide bond linkages. Synthesis of HA-IBO conjugate (HB) was confirmed by FT-IR and agarose gel electrophoresis with Stains-All staining. After hybridization of HB with i-motif ODN (IMO), it was confirmed that doxorubicin (DOX) could be loaded in HB-IMO hybrid structure (HBIM) with 65.6% of drug loading efficiency (DLE) and 25.0% of drug loading content (DLC). At pH 5.5, prompt and significant DOX release from HBIM was observed due to the disruption of HBIM hybrid structure via i-motif formation of IMO, contrary to pH 7.4 condition. Then, HBIM was complexed with low molecular weight polyethylenimine (PEI1.8k), forming positively charged nanostructures (Z-average size: 126.0 ± 0.4 nm, zeta-potential: 16.1 ± 0.3 mV). DOX-loaded HBIM/PEI complexes displayed higher anticancer efficacy than free DOX in A549 cells, showing the potential for pH-responsive anticancer drug delivery systems.

Antiproliferative effects of new magnetic pH-responsive drug delivery system composed of Fe3O4, CaAl layered double hydroxide and levodopa on melanoma cancer cells

In this study, an efficient drug delivery system composed of Fe3O4, CaAl layered double hydroxide (LDH) and l-Dopa has been synthesized through hydrogen bonds between l-Dopa and CaAl-LDH encapsulated Fe3O4 nanoparticles (Fe3O4@CaAl-LDH@l-Dopa). The structural features of Fe3O4@CaAl-LDH@l-Dopa were characterized using XRD, SEM, TEM, EDX, FT-IR, VSM, TGA, XPS, zeta potential analysis and BET. All of the characterization techniques show the uniform high surface area core-shell structure with about 120 nm in average size. Also, the obtained results clearly indicate that this drug delivery system possess high potent for adsorption of l-Dopa (52 wt%) and high drug encapsulation efficiency (71%). The amount of l-Dopa release in low pHs (53.8%) which simulates the environment of cancer cells is greater than higher pHs. The in vitro cytotoxic and anticancer activities of Fe3O4@CaAl-LDH@l-Dopa were investigated against Mel-Rm Cells Melanoma (NCIt: C3224) using LDH colorimetric assay and differential staining cell death assay. The results showed Fe3O4@CaAl-LDH@l-Dopa with a lower concentration of l-Dopa, illustrate a higher cytotoxicity and anticancer activity.

Reversible 2D networks of oligo(ε-caprolactone) at the air–water interface

Hydroxyl terminated oligo(ε-caprolactone) (OCL) monolayers were reversibly cross-linked forming two dimensional networks (2D) at the air–water interface. The equilibrium reaction with glyoxal as the cross-linker is pH-sensitive. Pronounced contraction in the area of the prepared 2D OCL films in dependence of surface pressure and time revealed the process of the reaction. Cross-linking inhibited crystallization and retarded enzymatic degradation of the OCL film. Altering the subphase pH led to a cleavage of the covalent acetal cross-links. The reversibility of the covalent acetal cross-links was proved by observing an identical isotherm as non-cross-linked sample. Besides as model systems, these customizable reversible OCL 2D networks are intended for use as pH responsive drug delivery systems or functionalized cell culture substrates.

Fabrication and characterization of hydroxyapatite/sodium alginate/chitosan composite microspheres for drug delivery and bone tissue engineering

Hydroxyapatite/sodium alginate/chitosan (HA/SA/CS) composite microspheres, which possess good biocompatibility for specific biomedical application, were prepared using an emulsion crosslink technique; calcium ions were used as a cross-linking agent. The effect of the concentration of sodium alginate (SA), the volume ratio of water to oil, the content of hydroxyapatite (HA) nanoparticles, as well as rotation speed, on the morphology and dispersion of composite microspheres were investigated. Also investigated were the drug loading, release behaviors, in vitro hemolysis activity, cytotoxicity, cell adhesion and proliferation capacity of the materials. The results demonstrate that the HA/SA/CS composite microspheres were successfully prepared; their drug loading and encapsulation efficiency are much higher than that of HA nanoparticles. Dox-loaded HA/SA/CS composite microspheres show good pH-sensitive drug-release capability. The hemolysis and cytotoxicity tests suggest that the microspheres have good blood and cell compatibility. Furthermore, the prepared composite microspheres display better cell adhesion and proliferation capacity than HA nanoparticles and HA/SA composite microspheres. Therefore, the HA/SA/CS composite microspheres might have potential as drug carriers in a pH-responsive controlled-release drug delivery system and as candidates for application in bone tissue engineering.

Development of MCM-41 mesoporous silica nanoparticles as a platform for pramipexole delivery

Herein, we present development of new pH-responsive drug delivery systems for D3-dopamine receptor agonist pramipexole, based on its encapsulation in MCM-41 mesoporous silica particles. Pramipexole loaded particles were further coated with chitosan and/or sodium alginate in order to modify drug release. The prepared pramipexole loaded nanoparticles were characterized by using X-ray diffraction (XRD), N2-physisorption, dynamic light scattering (DLS), TEM and attenuated total reflection infrared (ATR-FTIR) spectra. The post-coating of pramipexole loaded MCM-41 with chitosan/sodium alginate polymers changed dramatically physicochemical properties of the particles. The release profile showed that combination of both polymers led to significant reduction by approximately 50% in the initial burst-release effect at both tested pH values (1.2 and 6.8). Uncoated MCM-41 released the total amount of pramipexole within the first 15 min, whereas double-coated particles reached full release after 300 min. Interestingly, we found that pramipexole loaded MCM-41 particles showed a higher potential in preventing H2O2-induced oxidative damage in human neuroblastoma SH-SY5Y cells, compared to the free drug. In conclusion, pramipexole loading in chitosan/sodium alginate coated MCM-41 might represent a promising drug delivery strategy for modified release and neuronal protection against oxidative damage, observed in Parkinson's disease.

Rational design of a multi-responsive drug delivery platform based on SiO2@PPy@poly(acrylic acid-co-acrylamide)

Poly(acrylic acid-co-acrylamide) (P(AA-co-AM)) hydrogels with upper critical solution temperature (UCST) were synthesized via radical copolymerization technology, which were then incorporated with SiO2@polypyrrole (SiO2@PPy) for the construction of light-, thermo- and pH-responsive drug delivery system. The synthesized SiO2@PPy@P(AA-co-AM) hydrogels were then examined by Fourier transform infrared (FT-IR) spectrometry, field emission scanning electron microscopy (FESEM), thermogravimetry (TG) and differential thermogravimetric (DTG). Finally, the designed SiO2@PPy@P(AA-co-AM) hydrogels were used for controlled delivery of 5-fluorouracil (5-FU), an anti-cancer drug. An encapsulation ratio of up to 92.2% was obtained when 5-FU was encapsulated in the SiO2@PPy@P(AA-co-AM) hydrogels, and the cumulative release of 5-FU could reach 83.9% with the near-infrared (NIR) irradiation of 6 h at pH 7.4. During the controlled release of 5-FU, PPy in the system could convert the NIR irradiation to heat as a photo-thermal transducer while maintaining the temperature in the UCST range of P(AA-co-AM). In addition, SiO2 in the hydrogels acted as a gatekeeper to prevent the burst release of 5-FU.

Facile development, characterization, and evaluation of novel bicalutamide loaded pH-sensitive mesoporous silica nanoparticles for enhanced prostate cancer therapy

It is a challenge to deliver therapeutics exclusively to cancer cells, while sparing the normal cells. However, pH-sensitive delivery systems have proved to be highly efficient in fulfilling this task due to their ability to provide on-demand and selective release of drug at acidic tumor sites. As a proof of concept, here pH responsive drug delivery system based on mesoporous core shell nanoparticles (NPs) surrounded with poly acrylic acid (PAA) layers were prepared employing a facile synthesis strategy. Bicalutamide (BIC) was encased into surface functionalized MCM-41 nanoparticles via electrostatic interactions. The synthesized NPs were characterized by nitrogen adsorption and desorption isotherms, SEM-EDS, TEM, LXRD, and WXRD. In vitro release studies demonstrated that BIC-MSN-PAA NPs exhibited a higher release in the acidic media which varied inversely with the increase in pH. Further, the results of cell cytotoxicity assay were evident that BICMSNs exhibited more potent killing of both PC-3 and LNCaP cells than free BIC. PAA-MSNs also exhibited an enhanced cellular uptake and prolonged circulation time in vivo. The results are suggestive of the fact that PAA functionalized MSNs can serve as an effective pH-responsive template and hold a great potential ahead in controlled release and effective cancer treatment.

PH-responsive controlled release of mesoporous silica nanoparticles capped with Schiff base copolymer gatekeepers: Experiment and molecular dynamics simulation.

In this study, Schiff-base copolymer coating and mesoporous silica nanoparticles (Polymer@MSN) were synthesized by ARGET ATRP and sol-gel method respectively. Imine bonds acted as the pH-cleavable linker between copolymer gatekeepers and MSN to promote the controlled-release performance of DOX. The DOX-loaded nanoparticles (Polymer@MSN-DOX) were spherical with a diameter of approximately 150 nm. At pH 5.0 (pH of intracellular environment), the cumulative release of DOX within 72 h was 45% higher than that at pH 7.4 (normal physiological environment) due to the cleavage of imine bonds, showing obvious pH-responsive drug release performance. Confocal microscopy studies and in vitro cytotoxicity results revealed that Polymer@MSN-DOX could smoothly enter HepG2 cells to release DOX and show a high cytotoxicity. Noted specially that molecular dynamics simulations were applied to investigate the microcosmic adsorption/diffusion interaction between drug molecules and MSN. Simulation results showed that the driving force of DOX adsorption in mesoporous channels was originated from hydrogen bonding interaction between the mesoporous wall and DOX molecules and π-π conjugated interaction between benzene rings in addition to concentration differences. The structural design of composite nanocarriers in this research could provide guidance for the application of pH-responsive MSN-based drug delivery system.

OFF–ON nanodiamond drug platform for targeted cancer imaging and therapy

The pH-responsive drug delivery system (NPGD) can act as a direct OFF–ON mechanism for activatable bioimaging and cancer therapy.