Research progress of tumor immunomodulation strategies based on nanodrug delivery system / 中国药科大学学报

@#Tumor immunotherapy is a therapeutic modality that uses immunological principles and methods to activate and enhance the body''s immune system to generate immune response for the removal of tumour cells. Many new immunotherapeutic agents have demonstrated effective anti-tumour capabilities, yet their clinical use is challenging due to the complex mechanisms of tumour immune escape. Meanwhile, these drugs would accumulate in different tissues and organs in the human body and be unable to achieve precise and specific targeting therapeutic effects, resulting in serious immune-related adverse effects, which greatly hinders the clinical potential of immunotherapy.Nanodrug delivery systems can deliver immunotherapeutic drugs to target tissues or specific immune cells precisely, thereby enhancing immune effects and reducing side effects.This paper reviews the research progress of nanodrug delivery systems in tumour immunotherapy in recent years based on the regulatory mechanism of the anti-tumour immune response, with a prospect of the challenges and development in this field.

Tumor-targeting intravenous lipid emulsion of paclitaxel:Characteristics,stability,toxicity,and toxicokinetics / 药物分析学报

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for drug delivery

High-density lipoproteins (HDL) are naturally-occurring nanoparticles that are biocompatible, non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and microRNA from donor cells to recipient cells. Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins (rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative, promising avenue for efficient targeting transport of nanomedicine.