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Qing Zhang,1,* Wenjun Hu,1,* Mingxue Guo,1 Xinyu Zhang,1 Qin Zhang,1 Fengqi Peng,1 Liwen Yan,1 Zucheng Hu,1 Jakkree Tangthianchaichana,2 Yan Shen,3 Haiyan Hu,4 Shouying Du,1 Yang Lu1 1School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China; 2Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand; 3School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 4School of Pharmacy, Beijing Health Vocational College, Beijing, 101100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyan Hu, School of Pharmacy, Beijing Health Vocational College, Beijing, 101100, People’s Republic of China, Email yxyhhy@163.com Yang Lu, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email luyang@bucm.edu.cnIntroduction: Responsive drug delivery systems hold great promise for tumor treatment as they focus on therapeutic agents directly, thus minimizing systemic toxicities and drug leakage. In this study, we covalently bound a matrix metalloproteinases-2 (MMP-2) enzyme-sensitive peptide to a tissue-penetrating peptide to rationally design a MMP-2 responsive multifunctional peptide hydrogel platform (aP/IR@FMKB) for cancer photothermal-chemo-immunotherapy. The constructed aP/IR@FMKB with bufalin (BF) loaded in trimethyl chitosan nanoparticles (TB NPs), photothermal agent IR820, and immune checkpoint inhibitor aPD-L1 by self-assembly could be dissociated in the presence of MMP-2 enzyme, triggering content release.Methods: TB NPs, IR820, and aPD-L1 were encapsulated by intermolecular self-assembly and enzyme-sensitive nanogels (aP/IR@FMKB) were constructed. The in vitro cytotoxicity of the blank gels and their ability to induce immunogenic cell death (ICD) in aP/IR@FMKB were evaluated using 4T1 cells. The promotion of dee

Ziyi Dong,1,2 Xinyu Zhang,1 Qing Zhang,1 Jakkree Tangthianchaichana,1,3 Mingxue Guo,1 Shouying Du,1 Yang Lu1 1Laboratory of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Research and Development Centre in Beijing, CSPC Pharmaceutical Group Limited, Beijing, People’s Republic of China; 3Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, ThailandCorrespondence: Yang Lu; Shouying Du, Beijing University of Chinese Medicine, Number 11 East Section of the North Third Ring Road, Beijing, 100029, People’s Republic of China, Tel + 86-10-84738615, Email luyang@bucm.edu.cn; dumenzidi123@163.comAbstract: Traditional chemotherapy is one of the main methods of cancer treatment, which is largely limited by severe side effects and frequent development of multi-drug resistance by cancer cells. Antimicrobial peptides (AMPs) with high efficiency and low toxicity, as one of the most promising new drugs to replace chemoradiotherapy, have become a current research hotspot, attracting the attention of worldwide researchers. AMPs are natural-source small peptides from the innate immune system, and certain AMPs can selectively kill a broad spectrum of cancer cells while exhibiting less damage to normal cells. Although it involves intracellular mechanisms, AMPs exert their anti-cancer effects mainly through membrane destruction effect; thus, AMPs also hold unique advantages in fighting drug-resistant cancer cells. However, the poor stability and hemolytic toxicity of peptides limit their clinical application. Fortunately, functionalized nanoparticles have many possibilities in overcoming the shortcomings of AMPs, which provides a huge prospect for better application of AMPs. In this paper, we briefly introduce the characteristics and different sources of AMPs, review and summarize the mechanisms of action and the research status of AMPs used as an anticancer th

Ziyi Dong,* Qing Zhang,* Changhai Wang, Wenjun Hu, Xianglong Yu, Mingxue Guo, Xinyu Zhang, Meng Sun, Shouying Du, Yang Lu School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shouying Du, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email dumenzidi123@163.com Yang Lu, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email landocean28@163.comIntroduction: Chemotherapeutic drugs are often ineffective due to the delivery. Local chemotherapy, which has high drug concentration, low systemic toxicity, and long duration, has shown excellent potential. Cationic antimicrobial peptides have been proved to enhance the tumor cells’ uptake of chemotherapeutic drugs through the membrane-breaking effect. In this study, we designed and developed a thermosensitive gel co-loaded with Dermaseptin-PP and paclitaxel liposomes to increase local chemotherapy.Methods: The paclitaxel liposomes were prepared. Then, it was co-loaded with Dermaseptin-PP in a poloxamer-based thermosensitive gel to obtain Dermaseptin-PP/paclitaxel liposomes gel. The thermosensitivity of gels was investigated by test tube inversion method. The rheology was tested by rheometer. The in vitro cytotoxicity and the permeation in tumor of gels were examined by H157 cells and the 3D cell model, respectively. The retention in tumor and antitumor activity of gels were evaluated by H157 tumor-bearing nude mice.Results: The particle size of paclitaxel liposomes was 148.97 ± 0.21 nm. The encapsulation rate was 86.1%, and the drug loading capacity was 19.4%. The gels had slow-release and temperature-sensitive properties. The porous 3D network structure of the gels could ensure that the drug was fixed into the tumor. In vitro and in vivo distribu