Changchun Wang

Synergistic Cisplatin/Doxorubicin Combination Chemotherapy for Multidrug-Resistant Cancer via Polymeric Nanogels Targeting Delivery

Combination chemotherapy has been proposed to achieve synergistic effect and minimize drug dose for cancer treatment in clinic application. In this article, the stimuli-responsive polymeric nanogels (<100 nm in size) based on poly(acrylic acid) were designed as codelivery system for doxorubicin and cisplatin to overcome drug resistance. By chelation, electrostatic interaction, and π-π stacking interactions, the nanogels could encapsulate doxorubicin and cisplatin with designed ratio and high capacity. Compared with free drugs, the nanogels could deliver more drugs into MCF-7/ADR cells. Significant accumulation in tumor tissues was observed in the biodistribution experiments. The in vitro antitumor studies demonstrated the superior cell-killing activity of the nanogel drug delivery system with a combination index of 0.84, which indicated the great synergistic effect. All the antitumor experimental data revealed that the combination therapy was effective for the multidrug-resistant MCF-7/ADR tumor with reduced side effects.

Electrochemical Doping of Halide Perovskites with Ion Intercalation

Halide perovskites have recently been investigated for various solution-processed optoelectronic devices. The majority of studies have focused on using intrinsic halide perovskites, and the intentional incoporation of dopants has not been well explored. In this work, we discovered that small alkali ions, including lithium and sodium ions, could be electrochemically intercalated into a variety of halide and pseudohalide perovskites. The ion intercalation caused a lattice expansion of the perovskite crystals and resulted in an n-type doping of the perovskites. Such electrochemical doping improved the conductivity and changed the color of the perovskites, leading to an electrochromism with more than 40% reduction of transmittance in the 450-850 nm wavelength range. The doped perovskites exhibited improved electron injection efficiency into the pristine perovskite crystals, resulting in bright light-emitting diodes with a low turn-on voltage.

Preparation of Pt(IV)-crosslinked polymer nanoparticles with an anti-detoxifying effect for enhanced anticancer therapy

Cisplatin is a widely-used chemotherapeutic drug in the clinic against a range of cancers. However, its anti-cancer efficacy and bioavailability are severely affected by systemic toxicity as well as drug resistance, which are mainly due to indiscriminate body distribution, low tumor accumulation and glutathione (GSH)-related drug detoxification. In this study, we prepared for the first time a new kind of Pt(IV)-crosslinked polymer nanoparticle with small, uniform size and high loading of cisplatin (60.8%). Such a kind of polymer nanodrug could keep its structural integrity during blood circulation to afford higher tumor accumulation via the EPR effect and receptor-mediated targeting effect, yet rapidly self-disintegrate to release drugs in response to tumor intracellular bio-reducing molecules, such as glutathione (GSH), resulting in efficient cancer cell inhibition and reduced systemic toxicity in vivo. Meanwhile, some of the cellular GSH molecules are depleted and transformed into an oxidized GSSG form to decrease their chelating interaction with platinum drugs, which attenuate their detoxifying effect on the Pt(II) species and may have an advantage for overcoming the tumor resistance to cisplatin induced by GSH. Moreover, the maximum tolerated dose of drug could be greatly enhanced (>3 fold), which improved the bioavailability of the nanodrug at relatively high doses. The present work provides a novel drug self-crosslinked design tactic and might open a new window for clinical cancer treatment.

Micron-sized surface enhanced Raman scattering reporter/fluorescence probe encoded colloidal microspheres for sensitive DNA detection

A new type of optical probes, featuring surface enhanced Raman scattering (SERS) and fluorescence spectra dual-mode encoding, has been reported in this article. Based on the uniform micrometer-sized melamine resin/Ag nanoparticles (MRM/Ag-NPs) composite microspheres, the SERS reporters and fluorescent probes were successfully fixed onto the different layers of the MEM/Ag-NPs microspheres, which supported the sensitive DNA detecton. The two spectroscopic methods commonly considered to be contradictive to each other, yet the optical signals were separable in the experiments. The dual-encoding strategy and single microsphere detecton method put the number of available independent codes to be rough the multiple of those available in the two optical detection channels, which increases far more rapidly than the summation of the two channels. As a proof of cencept, the utility of this dual spectrum mode SERS-fluoresecence encoded microsphere (SFEM) was demonstrated in a specific DNA detection using complimentary ssDNA functionalized magnetic beads as the DNA capturing and separation agents. Excellent encoding results were demonstrated from the decoding of the SERS and fluorescence signals of the SFEM. The method appears to be general in scope and we expect that the SERS-fluoresecence encoded microspheres system is applicable to multiplex bioassays of a variety of biomolecules.

Flexible assembly of targeting agents on porous magnetic nano-cargos by inclusion complexation for accurate drug delivery

Efficient delivery of anticancer drugs to increase the intracellular drug concentration in targeted tissues is urgently needed in cancer chemotherapy, since clinical drugs usually have serious side effects on normal tissues. In this paper, we developed a new method to fabricate multi-functional porous magnetic nano-cargos by grafting PEG/folate onto the surface and storing doxorubicin in the pores of magnetic supraparticles for accurate delivery of anticancer drugs. The anticancer drug doxorubicin was fixed into the porous magnetic cores with acid-sensitive linkers, which can be broken in acidic intracellular environments or organelles; the superficial PEG chains on the magnetic cores not only enhanced the dispersion stability of the nano-cargos but also immobilized folate modified α-cyclodextrin by inclusion complexation, and the α-cyclodextrin derivatives could be flexibly replaced as needed. Remarkable proliferation inhibition of cancer cells and minor side effects on normal cells were achieved due to the controlled drug release manner of the nano-drug system, indicating that this kind of nano-cargo has great potential in cancer chemotherapy for personalized and accurate treatment.

Biodegradable yolk-shell microspheres for ultrasound/MR dual-modality imaging and controlled drug delivery

A new class of uniform biodegradable yolk-shell Fe3O4@PFH@PMAA-DOX microspheres was developed as ultrasound/MR dual-modality imaging contrast agents and drug delivery system. PMAA shells exhibit excellent drug loading capability and efficiency, the DOX-loading capacity is 15.4wt% and the drug loading efficiency is 91%. In vivo ultrasound and MRI experiments indicate that the as-prepared Fe3O4@PFH@PMAA-DOX microspheres successfully reach tumor tissues and possess robust dual-modality imaging capability, the r2 value of MRI is 71.82mM-1s-1. In vitro cytotoxicity and in vivo tissues biopsies show that the loaded DOX can be control-released under pH, redox and ultrasound multi-stimuli and kill cancer cells effectively. Furthermore, disulfide-crosslinked PMAA shells and PGA-stabilized Fe3O4 cores can be respectively degraded into short hydrophilic polymer chains and iron ions, reducing their cumulative toxicity in organisms. Thus, the multifunctional biodegradable microspheres are safer for normal tissues and more beneficial in actual clinical applications.

Role of Protecting Groups in Synthesis and Self-Assembly of Glycopolymers.

Protection and deprotection are basic procedures in oligosaccharide synthesis. By taking advantage of the processes of attaching and removing the protecting groups, preparation of oligosaccharides with complex structures can be achieved with relatively high yields. However, the role of protecting groups in solution properties and self-assembly of synthetic glycopolymers has been overlooked in the literature. In this paper, we focused on such effects for well-designed copolymers in which different numbers of benzyl (Bn) groups are installed regioselectively in saccharide rings. Thus, three block copolymers P1, P2, and P3 composed of a common block of PNIPAm and a glycopolymer block with trisaccharide triMan side chains differing in the respective number of Bn (0, 2, and 6) were prepared. The solutions of these block copolymers in water were investigated by dynamic and static light scatting and VT-1H NMR. We found that all of the three copolymers P1, P2, and P3 formed association at room temperature. Particularly, P1 associated loosely due to carbohydrate-carbohydrate interaction (CCI) while P3 formed tight aggregates due to hydrophobic interactions between Bn, and P2 behaved between those of P1 and P3. Moreover, upon heating, phase transition of PNIPAm block took place leading to micelle formation. Hydrodynamic radius of P1 and P2 increased significantly as expected, while P3 did not follow this trend, because during heating, collapse and accumulation of the PNIPAm chains would occur within the tight aggregates mainly, so it leads to a little change of the size.

Morphology-Controlled Coating of Colloidal Particles with Silica: Influence of Particle Surface Functionalization

We present a general, convenient, and efficient synthetic concept for the coating of colloidal particles with a silica (SiO2) shell of well-defined and precisely controlled morphology and porosity. Monodisperse submicroscopic polystyrene (PS) particles were synthesized via two-stage emulsifier-free emulsion polymerization and subsequent swelling polymerization, enabling selective particle surface modification by the incorporation of ionic (methacrylic acid, MAA) or nonionic (hydroxyethyl methacrylate, HEMA or methacrylamide, MAAm) comonomers, which could be proven by zeta potential measurements as well as by determining the three-phase contact angle of the colloidal particles adsorbed at the air-water and n-decane-water interface. The functionalized particles could be directly coated with silica shells of variable thickness, porosity, and controlled surface roughness in a seeded sol-gel process from tetraethoxysilane (TEOS), leading to hybrid PS@silica particles with morphologies ranging from core-shell (CS) to raspberry-type architectures. The experimental results demonstrated that the silica coating could be precisely tailored by the type of surface functionalization, which strongly influences the surface properties of the colloidal particles and thus the morphology of the final silica shell. Furthermore, the PS cores could be easily removed by thermal treatment, yielding extremely uniform hollow silica particles, while maintaining their initial shell architecture. These particles are highly stable against irreversible aggregation and could be readily dried, purified, and redispersed in various solvents. Herein we show a first example of coating semiconducting CdSe/ZnS nanocrystals with smooth and spherical silica shells by applying the presented method that are expected to be suitable systems for applications as markers in biology and life science by using fluorescence microscopy methods, which are also briefly discussed.

Targeted Soft Biodegradable Glycine/PEG/RGD-Modified Poly(methacrylic acid) Nanobubbles as Intelligent Theranostic Vehicles for Drug Delivery

The development of multifunctional ultrasound contrast agents has inspired considerable interest in the application of biomedical imaging and anticancer therapeutics. However, combining multiple components that can preferentially accumulate in tumors in a nanometer scale poses one of the major challenges in targeting drug delivery for theranostic application. Herein, reflux-precipitation polymerization, and N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide-meditated amidation reaction were introduced to effectively generate a new type of soft glycine/poly(ethylene glycol) (PEG)/RGD-modified poly(methacrylic acid) nanobubbles with a uniform morphology and desired particle size (less than 100 nm). Because of the enhanced biocompatibility resulting from the glycine modification, over 80% of the cells survived, even though the dosage of glycine-modified polymeric nanobubbles was up to 5 mg/mL. By loading doxorubicin as an anticancer drug and perfluorohexane as an ultrasound probe, the resulting glycine/PEG/RGD-modified nanobubbles showed remarkable cancer therapeutic efficacy and a high quality of ultrasonic imaging; thus, the ultrasonic signal exhibited a 1.47-fold enhancement at the tumor site after intravenous injection. By integrating diagnostic and therapeutic functions into a single nanobubble, the new type of theranostic nanobubbles offers a promising strategy to monitor the therapeutic effects, giving important insights into the ultrasound-traced and enhanced targeting drug delivery in biomedical applications.

Preparation of MRI-visible gadolinium methacrylate nanoparticles with low cytotoxicity and high magnetic relaxivity

A new convenient and easy-scalable one-step synthetic strategy to achieve metal-containing polymer nanoparticles for applications as magnetic resonance imaging contrast agent is reported. In this study, a novel contrast agent based on poly(gadolinium methacrylate) (poly(Gd(MAA)3)) nanoparticles was prepared by one-step aqueous dispersion polymerization of gadolinium methacrylate monomer (Gd(MAA)3), whereby stable particles were obtained due to the association of GdIII with the polymer carboxylate anions, which provided latent crosslinking of the polymer nanoparticles without the addition of further crosslinking reagents. The morphology and final composition of the corresponding nanoparticles was thoroughly characterized and their cytotoxicity as well as their potential use in MRI was evaluated in vitro on HEK 293T cells by using the CCK-8 assay. The presented results demonstrated, that the poly(Gd(MAA)3) nanoparticles had a spherical morphology with mesoporous substructure, a sufficiently low cytotoxicity and an exceptionally high longitudinal relaxivity of r1xa0=xa012.613xa0mM−1xa0s−1, making these nanoparticles excellent candidates for in vivo imaging systems. Herein described poly(Gd(MAA)3) nanoparticles can be valuable in a wide range of biomedical applications with simultaneous bioconjugation, drug delivery as well as imaging capabilities for the early detection of lesions of the brain and the central nervous system, for assessing cardiac function, and for detecting tumors.