Hongshuai Wu

Near-Infrared Light and pH Dual-Responsive Targeted Drug Carrier Based on Core-Crosslinked Polyaniline Nanoparticles for Intracellular Delivery of Cisplatin

Biodegradable polymeric nanoparticles have received growing interest as one of the most promising agents for drug delivery. In the present work, functional and core-crosslinked poly(ethylene glycol) with poly(ϵ-caprolactone) (PEG5k -PCL10k ) block copolymer and lecithin as biodegradable polymer doped with polyaniline was used to assemble nanoparticles which were prepared for targeted delivery and controlled release of cisplatin. The morphology of the polyaniline nanoparticles was determined by dynamic light scattering and the prepared nanoparticles showed a size of 83(±1) nm and a uniform spherical shape. For targeting to HER2 receptors, Herceptin was applied to guide the nanoparticles to breast cancer cells. Studies on cellular uptake and drug release of the nanocarriers showed that the prepared nanoparticles were efficiently taken up by breast cancer cells and the drug was released efficiently under acidic conditions when exposed to a near-infrared laser (808 nm, 1.54 W) for 5 min. Our research highlights the great potential of near-infrared light and pH dual-responsive release by core-crosslinked nanoparticles in nanobiomedicine.

Near infrared radiated stimulus-responsive liposomes based on photothermal conversion as drug carriers for co-delivery of CJM126 and cisplatin

Synergistic therapy has caused increasing interest in recent treatment of cancer owing to its preferable therapeutic efficiency to most single antineoplastic protocol. Herein, we design a co-delivery two drugs nanosystem based on biodegradable liposomes, loading cisplatin, Indocyanine green (ICG), and CJM126 coupled with cholesterol derivative (CJM-Chol) for the purpose of synergistic therapy. The obtained nanoparticles showed a uniform diameter of 103.8nm and a favorable morphology. The investigation on near infrared radiated (NIR) responsive release showed that NIR mediated photothermal conversion induced a controllable drug release from liposomes. Furthermore, the designed liposomes (only 50μg/mL) displayed an inspiring photothermal conversion efficiency and received a high temperature (65.6°C, Tm=42°C) when exposed to an 808nm near infrared laser (1.54W, 5min). Besides, it turned out that the delivery system could be efficiently endocytosed by tumor cells, which attributed to its admirable biocompatibility and the targeting role of folate. The prepared nanoparticles showed significantly excellent inhibitory effect (3.05% cell viability in 24h) on MDA-MB-231 cells when added irradiation as compared with free cisplatin (28.41%) or treatment without NIR (11.24%) in our study. Our research highlights the present nanoparticles provide a promising strategy for targeted delivery and photothermal treatment.

Co-delivery of cisplatin and CJM-126 via photothermal conversion nanoparticles for enhanced synergistic antitumor efficacy

Polymeric biomaterials that can be smartly disassembled through the cleavage of the covalent bonds in a controllable way upon an environmental stimulus such as pH change, redox, special enzymes, temperature, or ultrasound, as well as light irradiation, but are otherwise stable under normal physiological conditions have attracted great attention in recent decades. The 2-(4-aminophenyl) benzothiazole molecule (CJM-126), as one of the benzothiazole derivatives, has exhibited a synergistic effect with cisplatin (CDDP) and restrains the bioactivities of a series of human breast cancer cell lines. In our study, novel NIR-responsive targeted binary-drug-loaded nanoparticles encapsulating indocyanine green (ICG) dye were prepared as a new co-delivery and combined therapeutic vehicle. The prepared drug-loaded polymeric nanoparticles (TNPs/CDDP-ICG) are stable under normal physiological conditions, while burst drugs release upon NIR laser irradiation in a mild acidic environment. The results further confirmed that the designed co-delivery platform showed higher cytotoxicity than the single free CDDP due to the synergistic treatment of CJM-126 and CDDP in vitro. Taken together, the work might provide a promising approach for effective site-specific antitumor therapy.

Synthesis and biological evaluation of redox/NIR dual stimulus-responsive polymeric nanoparticles for targeted delivery of cisplatin

Functional drug delivery systems enabling various favorable characteristics including specific targets, efficient cellular uptake and controllable release. At present work, a folate and cRGD dual modified nanoparticles based on NIR light and glutathione dual stimuli-responsive release system was successfully prepared and which simultaneously deliver cisplatin and ICG to tumor sites to enhance controllability. The prepared nanoparticles showed a stable uniform spherical morphology of 77.59 nm particle size range in PBS (pH = 7.4, 25 °C) and the encapsulated cisplatin were rapidly released in acidic environment especially added glutathione (GSH) and NIR irradiation. Moreover, the prepared nanoparticles can be efficiently internalized by tumor cells through the enhanced dual targeted ligands (folate and cRGD) for ICG imaging. The cytotoxicity assays showed that the cells viability decreased to 1.95% (SGC-7901) when been exposed to NIR light, and which further decreased to 1.25% in MCF-7 cells. Thus, the prepared nanoparticles showed excellent performance for photothermal conversion therapy of tumor cells and especially on human breast tumor cells. Our research highlights the great potential of stimuli-responsive smart nanoparticles in biomaterial and nano-biomedicine.

A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles

Abstract The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

FA and cRGD dual modified lipid-polymer nanoparticles encapsulating polyaniline and cisplatin for highly effective chemo-photothermal combination therapy

Abstract A combination of chemotherapy and photothermal therapy as a promising strategy has exhibited noticeable therapeutic effect on cancer therapy. To ensure the exertion of synergistic effect on a tumor region, a multifunctional vehicle for selectively delivering therapeutic agent into tumor cells is highly desirable. Thus, folate-poly (ethylene glycol)-distearoylphosphatidylcholine (FA-PEG-DSPE), cRGD [cyclic (Arg-Gly-Asp-D-Phe-Lys)]-PEG-DSPE and lecithin were employed to develop dual modified nanoparticles (FA/cRGD-PNPs) encapsulating polyaniline and cisplatin by a film-ultrasonic dispersion method. The FA/cRGD-PNPs showed a uniform size of 102.7 nm, remarkable stability and monodispersity, and highly localized temperature respond. Compared to chemo or photothermal treatment alone, the combined treatment on cells in vitro significantly suppressed the survival rate of MDA-MB-231 cells (1.87%) and MGC-803 cells (2.37%) treated for 48 h. The results further indicated the induced cell apoptosis rate of MDA-MB-231 cells reached to 92.6% with treatment for 24 h. Hence, our research highlights the great potential in drug delivery and the combination of chemotherapy and photothermal therapy.

Single-Layered Two-Dimensional Metal–Organic Framework Nanosheets as an in Situ Visual Test Paper for Solvents

Through a facile-operating ultrasonic force-assisted liquid exfoliation technology, the single-layered two-dimensional (2D) [Co(CNS)2(pyz)2] n (pyz = pyrazine) nanosheets, with a thickness of sub-1.0 nm, have been prepared from the bulk precursors. The atomically thickness and the presence of abundant sulfur atoms with high electronegativity arrayed on the double surfaces of the sheets are making this kind of 2D MOF (metal-organic framework) nanosheets highly sensitive to intermolecular interactions. As a result, it can be well dispersed in all kinds of solvents to give a stable colloidal suspension that can be maintained for at least one month, accompanied by significant solvatochromic behavior and various optical properties, which thus have shown the potential to be practically applicated as in situ visual test paper for solvent identification and solvent polarity measurements. More importantly, combined with a smartphone, this kind of 2D-MOF nanosheets can be developed into in situ visual test paper to identify isomers and determine the polarity of mixed solvents quantitatively and qualitatively, suggesting the promising application of a portable, economical, and in situ visual test strategy in real world.

A novel near-infrared triggered dual-targeted nanoplatform for mitochondrial combined photothermal-chemotherapy of cancer in vitro

A combination of photothermal-chemotherapy has received widespread attention in drug delivery systems for cancer treatment. However, the combination therapy operated in subcellular organelles, such as mitochondria, has been rarely reported. Herein, we designed a novel near-infrared (NIR) triggered dual-targeted nanoplatform (FA/TPP-DINPs) based on mitochondrial combined photothermal-chemotherapy by co-loading FDA-approved NIR dye indocyanine green (ICG) and anticancer drug doxorubicin (DOX). The resulting nanoparticles showed a monodispersed sphere and excellent colloidal stability. Specially, the simultaneous introduction of targeted ligands folic acid (FA) and triphenylphosphine (TPP) to nanoparticles significantly promoted the cellular internalization and mitochondrial co-localization of nanoparticles. Moreover, the encapsulated dye could convert NIR light into heat with high efficiency, which makes the FA/TPP-DINPs an effective platform for mitochondrial combination therapy with chemotherapy drug DOX. Meanwhile, the thermal expansion in response to the change of temperature after sustained 808 nm laser irradiation could cause the disintegration of nanoparticles, which triggered the rapid release of DOX from nanoparticles. As expected, the prepared FA/TPP-DINPs exhibited evidently enhanced cytotoxicity and preeminent combination therapy efficiency on MCF-7 cells. Thus, the NIR triggered dual-targeted nanoplatform provides a new drug delivery strategy for mitochondrial combined photothermal-chemotherapy of cancer.

Cisplatin and Ce6 loaded polyaniline nanoparticles: An efficient near-infrared light mediated synergistic therapeutic agent

Lipid-polymer hybrid nanoparticle was suggested to be a new and promising drug delivery agent due to the suitable particle size and controllable release. However, the low drug loading capacity has been a critical problem in the improvement of the nano-carrier systems. At present work, we have designed and developed smart nanoparticles with cholesterol-cisplatin (IV) conjugate contained to enhance the drug loading capacity. The predesigned drug delivery system showed enhanced synergistic effect through co-delivery of cisplatin and Ce6 and the drug released in a controllable way due to the polyaniline mediated photothermal conversion. The prepared polyaniline nanoparticles showed a favorable particle size of 109.6 nm and spread harmoniously in aqueous solution. Moreover, the near infrared radiation (NIR) stimulus-responsive characteristic of the polyaniline nanoparticles prompts the release of cisplatin from the nanoparticles inside the cytoplasm and the αvβ3/αvβ5 integrins targeted ligands (cRGD) enhanced the cellular uptake of the polyaniline nanoparticles in receptor-overexpressing MCF-7 cells. Furthermore, the singlet oxygen generated by Ce6 further enhances the cytotoxicity and obtained the expected synergistic effect with cisplatin. Thus, the prepared cRGD-conjugated co-delivery of cisplatin and Ce6 polyaniline nanoparticles consider to be a promising nanoplatform in nano-biomedicine.

3-Nitroacridine derivatives arrest cell cycle at G0/G1 phase and induce apoptosis in human breast cancer cells may act as DNA-target anticancer agents

&NA; DNA is considered to be one of the most promising targets for anticancer agents. Acridine analogues have anticancer activity based on DNA binding and topoisomerases inhibition. However, due to the side effects, resistance and low bioavailability, a few have entered into clinical usage and the mechanisms of action are not fully understood. Novel acridine derivatives are needed for effective cancer therapy. A series of novel 3‐nitroacridine‐based derivatives were synthesized, their DNA binding and anticancer activities were evaluated. The chemical modifications at position 9 of the 3‐nitroacridine were crucial for DNA affinity, thus optimizing anticancer activity. UV–Vis and circular dichroism (CD) spectroscopy indicated interaction of compounds with DNA, and the binding modes were intercalation and groove binding. MTT assay and clonogenic assay showed that compounds 1, 2 and 3 had obvious cell growth inhibition effect. They induced cell apoptosis in human breast cancer cells in a dose‐dependent manner, and exhibited anticancer effect via DNA damage as well as cell cycle arrest at G0/G1 phage. Using confocal fluorescent microscope, the apoptotic features were observed. The results suggested that compounds 1–3 with high DNA binding affinity and good inhibitory effect of cancer cell proliferation can be developed as prime candidates for further chemical optimization.