Chemoimmunotherapeutic Nanogel for Pre- and Postsurgical Treatment of Malignant Melanoma by Reprogramming Tumor-Associated Macrophages.

Surgery is the primary method to treat malignant melanoma; however, the residual microtumors that cannot be resected completely often trigger tumor recurrence, causing tumor-related mortality following melanoma resection. Herein, we developed a feasible strategy based on the combinational chemoimmunotherapy by cross-linking carboxymethyl chitosan (CMCS)-originated polymetformin (PolyMetCMCS) with cystamine to prepare stimuli-responsive nanogel (PMNG) owing to the disulfide bond in cystamine that can be cleaved by the massive glutathione (GSH) in tumor sites. Then, chemotherapeutic agent doxorubicin (DOX) was loaded in PMNG, which was followed by a hyaluronic acid coating to improve the overall biocompatibility and targeting ability of the prepared nanogel (D@HPMNG). Notably, PMNG effectively reshaped the tumor immune microenvironment by reprogramming tumor-associated macrophage phenotypes and recruiting intratumoral CD8+ T cells owing to the inherited immunomodulatory capability of metformin. Consequently, D@HPMNG treatment remarkably suppressed melanoma growth and inhibited its recurrence after surgical resection, proposing a promising solution for overcoming lethal melanoma recurrence.

Harnessing nanobiotechnology for cerebral ischemic stroke management.

Cerebral ischemic stroke remains one of the most serious neurological disorders that pose threats to human health, causing a large amount of long-term disability or even death throughout the world. Based on its physiologic and pathological features, there are limited available therapeutic options for effective ischemic stroke management. Encouragingly, a rapid advancement of nanobiotechnology is bringing new insights into exploring more alternative strategies against cerebral ischemic stroke, which can cleverly overcome the limitations related to conventional treatment methods. Therefore, this review focuses on the recent achievements of nanobiotechnology for ischemic stroke management, which emphasizes diverse targeted delivery strategies using various nanoplatforms including liposomes, micelles, polymeric nanoparticles, nanogels, inorganic nanomaterials, and cell-derived nano-vectors based on the pathophysiological features of ischemic stroke. Moreover, different therapeutic approaches against ischemic stroke such as neuroprotection, anti-inflammation, thrombolysis, increased blood-brain barrier penetration and reactive oxygen species scavenging are highlighted. Meanwhile, this review discusses how these versatile nanoplatforms were designed to assist in the treatment of ischemic stroke. Based on this, challenges, opportunities, and future perspectives using nanobiotechnology through rational design for effective ischemic stroke management are revealed.

[Study on the application of PEI for gene transfer in mouse skin tissue].

A reliable, low-cost, and highly efficient nonviral gene delivery system using lower molecular weight polyethylenimine (LMW-PEI) is provided. LMW-PEI was linked to an expressing plasmid with green fluorescence protein gene (gfp), the transfection activity mediated by PEIs were examined in the CM7721 cell line and the skin tissue of mouse, respectively. The cytotoxicity of PEIs, the localization and continuance time of gfp expressed in the skin tissue of mouse were also studied. Results showed that the transfection rate of gfp mediated by LMW-PEI in the CM7721 cell line was about 55% . However, with the increasing PEI molecular weight, the cytotoxicity of PEI increased, but its transfection activity decreased. The tissue transfection results showed that LMW-PEI induced a significant expression of the gfp in the cells of hair vesicle and sweat gland of mouse skin tissues following transfection of 24 h, and the expression of gfp lasted 7 - 9 d. When the tissue of mouse was treated with retinoic acid and nitrogenous ketone, respectively, gfp was transferred to the granule layer of mouse skin tissue. The LMW-PEI described here is a new, highly efficient vector; it would be a useful nonviral vector for gene delivery technology.