The design of multifunctional nanocarriers for the co-delivery of anticancer drugs and genetic agents offers an effective and promising strategy to combat multidrug-resistant cancer. Herein, we developed a simple and facile method to fabricate a drug-self-gated and pH-sensitive mesoporous silica vehicle as a “four-in-one” versatile co-delivery system, which possesses targeted chemo and gene therapy capability against multidrug-resistant cancer. P-gp siRNA molecules were loaded into the channels of mesoporous silica nanoparticles. A chemotherapeutic drug (DOX) was employed as a gatekeeper via a pH-sensitive benzoic–imine covalent bond. Folic acid conjugation onto the surface endowed this system with an excellent tumor-targeting effect, which was demonstrated by the cellular and tumor targeting assay. The effective downregulation of P-gp protein by the co-delivered P-gp siRNA was observed by western blotting. Both the in vitro cell viability study and in vivo tumor inhibition assay showed a synergistic effect in suppressing cancer cell proliferation. Therefore, this drug-self-gated nanosystem exhibited great potential for improved multidrug-resistant cancer treatment without any further potential risks of capping agents.

•A pH-sensitive drug delivery system of mesoporous silica nanoparticles was prepared.•MSNs were surface modified by polydopamine for controlled release of desipramine.•The nanocarriers have good cytotoxicity and ASM inhibit efficiency.•The novel drug delivery system is promising for cancer therapy.A novel pH-sensitive drug delivery system of mesoporous silica nanoparticles (MSNs) which were modified by polydopamine (PDA) for controlled release of cationic amphiphilic drug desipramine (DES) was prepared. MSNs–DES–PDA were characterized in terms of size, size distribution, surface morphology, BET surface area, mesoporous size and pore volume, drug loading content and in vitro drug release profile. MSNs–DES–PDA had high drug loading content and pH sensitivity. The DES release profiles of MSNs–DES and MSNs–DES–PDA were totally different, and the drug release of MSNs–DES–PDA accelerated with increasing acidity. MSNs–DES–PDA can be internalized into cells. In vitro experiments demonstrated that MSNs–DES–PDA had higher cytotoxicity and inhibitory effects on acid sphingomyelinase than those of free DES. This drug delivery system was beneficial for controlled release and cancer therapy.

A novel multifunctional material consisting of a four-armed star-shaped porphyrin-cored poly(lactide)-b-D-α-tocopheryl polyethylene glycol 1000 succinate amphiphilic copolymer (TAPP-PLA-b-TPGS) was synthesized through an arm-first approach and was characterized by 1H NMR and gel permeation chromatography (GPC). This porphyrin-functionalized material has potential applications in both drug-delivery systems and photodynamic therapy (PDT). Docetaxel (DTX)-loaded or coumarin 6-loaded nanoparticles (NPs) were prepared by a modified nanoprecipitation technique. The resulting NPs were characterized through determination of their size and size distribution data, surface charge and surface morphology, drug loading content, drug encapsulation efficiency, as well as differential scanning calorimetry (DSC) experiments. In drug release assays, the DTX-loaded NPs showed excellent pH-dependent drug-release behavior. The NPs were also found to generate singlet oxygen (1O2) species and exhibit significant phototoxicity in HeLa cervical cancer cells after irradiation with light of 660 nm wavelength. The drug-loaded NPs demonstrated superior performance compared to the commercial drug, Taxotere®, which is likely due to synergistic effects between phototherapy and chemotherapy in the destruction of HeLa cells. This novel functionalized drug-delivery system shows considerable potential in providing a new multi-modality treatment approach for cancer.

A star-shaped random copolymer, cholic acid functionalized poly(ε-caprolactone-ran-lactide)-b-poly(ethylene glycol) 1000 (CA-(PCL-ran-PLA)-b-PEG1k), was synthesized by a core-first approach involving three stages of chemical reactions, and was characterized by hydrogen-1 nuclear magnetic resonance (1H NMR), gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded nanoparticles (NPs) were prepared by a modified nano-precipitation method. The formation and characterization of these NPs were confirmed through dynamic light scattering, zeta potential measurements, field emission scanning electron microscopy, and transmission electron microscopy. The in vitro release profiles indicated that CA-(PCL-ran-PLA)-b-PEG1k NPs had excellent sustained and controlled drug release properties. Both confocal laser scanning microscope and flow cytometric results showed that the coumarin-6 loaded CA-(PCL-ran-PLA)-b-PEG1k NPs had the highest cellular uptake efficiency compared with PEG1k-b-(PCL-ran-PLA) NPs and CA-(PCL-ran-PLA) NPs in human hepatic carcinoma cells. The docetaxel-loaded CA-(PCL-ran-PLA)-b-PEG1k NPs were also proved to have the highest drug loading content, encapsulation efficiency, and the best anti-tumor efficacy both in vitro and in vivo. In conclusion, the star-shaped CA-(PCL-ran-PLA)-b-PEG1k copolymer was successfully synthesized and could be used as a promising drug-loaded biomaterial for liver cancer chemotherapy.

A novel of hydrophilic and polar N-vinylpyrrolidone modified post-crosslinked resin was synthesized and the adsorption behaviors toward puerarin from aqueous solution were investigated. The post-crosslinked adsorbent PNVP-DVBpc was prepared by Friedel–Crafts reaction of residual double bonds without external crosslinking agent. The specific surface area of precursor PNVP-DVB increased obviously after post-crosslinking modification. The synthesized adsorbents were characterized by BET surface area, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). The adsorption behaviors of puerarin from aqueous solution onto precursor PNVP-DVB and post-crosslinked adsorbent PNVP-DVBpc were thoroughly researched. Commercial polymeric adsorbents Amberlite XAD-4 and AB-8 were chosen as the comparison. Among the four media, PNVP-DVBpc presented the largest adsorption capacity of puerarin, which resulted from the synergistic effect of high specific surface area and polar groups (amide groups) onto the adsorbent matrix. Experimental results showed that equilibrium isotherms could be fitted by Freundlich model and the kinetic data could be characterized by pseudo-second order model reasonably. Column adsorption experiments indicated that the puerarin could be completely desorbed by 4.0 BV industrial alcohol. Continuous column adsorption–regeneration cycles demonstrated the PNVP-DVBpc without any significant adsorption capacity loss during operation.Graphical abstractHighlights► A novel of hydrophilic and polar post-crosslinked resin with high surface area was synthesized. ► SEM indicated that the precursor become more highly porous after the Friedel–Crafts modification. ► Post-crosslinked adsorbent showed the largest adsorption capacity of puerarin. ► The adsorption mechanism of puerarin was investigated.

The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in the docetaxel-resistant MCF-7 TAX30 human breast cancer cell line could be found in comparison with that of PLGA nanoparticles. In addition, the docetaxel-loaded PLGA/poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than that of docetaxel-loaded PLGA nanoparticles and Taxotere (P < .05). In conclusion, the results showed advantages of docetaxel-loaded PLGA nanoparticles incorporated with poloxamer 188 compared with the nanoparticles without incorporation of poloxamer 188 in terms of sustainable release and efficacy in breast cancer chemotherapy.From the Clinical EditorThe effects of poloxamer 188, a triblock copolymer were studied on nanoparticle morphology, size, cancer cell uptake and cytotoxicity. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in resistant human breast cancer cell line was demonstrated, resulting in a significantly higher level of cytotoxicity.

Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.

Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ε-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere®in the MCF-7 TAX30 cell culture, but the differences were not significant (p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere®(p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer.

Cervical cancer is caused by infection by high-risk human papillomavirus (HPV), especially HPV16. Limitations in current treatments of cervical cancers call for the development of new and improved immunotherapies. This study aims at investigating the efficacy of a novel vaccine consisting of modified HPV 16E7 fused with human cytotoxic T-lymphocyte antigen 4 (CTLA4). The regions in HPV16 E7 gene associated with its transformation and CTL-enhanced response were modified; the resultant HPV16mE7 was fused with extracellular region of CTLA4 to generate HPVml6E7-eCTLA4 fusion protein. Binding of this fusion protein to B7 molecules expressed on antigen presenting-cells (APCs) was demonstrated. C57BL/6 (H-2b) mice immunized with low dose of the fusion protein (10 μg) produced higher titer antibody and stronger specific CTL response, and expressed higher levels of IFN-γ and IL-12, compared with those immunized with HPVml6E7 only or admixture of HPVml6E7 and CTLA4, or PBS; and were protected from lethal dose tumor challenge. Tumor growth was retarded and survival prolonged in mouse models with the fusion protein treatment. Our results demonstrate that fusion of HPV16 E7 with eCTLA4 targeting APCs resulted in enhanced immunity, and that this fusion protein may be useful for improving the efficacy of immunotherapeutic treatments of cervical cancer and other HPV16 infection-associated tumors.

Despite setbacks in the past and apparent hurdles ahead, gene therapy is advancing toward reality. The past several years have witnessed this new field of biomedicine developing rapidly both in breadth and depth, especially for the treatment of cancer, thanks largely to the better understanding of molecular and genetic basis of oncogenesis and the development of new and improved vectors and technologies for gene delivery and targeting. This article is intended to provide a brief review of recent advances in cancer gene therapy using adenoviruses, both as vectors and as oncolytic agents, and some of the recent progress in the development of immunotoxins for use in cancer gene therapy.

A star-shaped random copolymer, cholic acid functionalized poly(ε-caprolactone-ran-lactide)-b-poly(ethylene glycol) 1000 (CA-(PCL-ran-PLA)-b-PEG1k), was synthesized by a core-first approach involving three stages of chemical reactions, and was characterized by hydrogen-1 nuclear magnetic resonance (1H NMR), gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded nanoparticles (NPs) were prepared by a modified nano-precipitation method. The formation and characterization of these NPs were confirmed through dynamic light scattering, zeta potential measurements, field emission scanning electron microscopy, and transmission electron microscopy. The in vitro release profiles indicated that CA-(PCL-ran-PLA)-b-PEG1k NPs had excellent sustained and controlled drug release properties. Both confocal laser scanning microscope and flow cytometric results showed that the coumarin-6 loaded CA-(PCL-ran-PLA)-b-PEG1k NPs had the highest cellular uptake efficiency compared with PEG1k-b-(PCL-ran-PLA) NPs and CA-(PCL-ran-PLA) NPs in human hepatic carcinoma cells. The docetaxel-loaded CA-(PCL-ran-PLA)-b-PEG1k NPs were also proved to have the highest drug loading content, encapsulation efficiency, and the best anti-tumor efficacy both in vitro and in vivo. In conclusion, the star-shaped CA-(PCL-ran-PLA)-b-PEG1k copolymer was successfully synthesized and could be used as a promising drug-loaded biomaterial for liver cancer chemotherapy.