title: Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy.
abstract: Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment.
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China.
authors: Bo
authors: B
authors: Zhang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China.
authors: Wei
authors: W
authors: Shi
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China.
authors: Ting
authors: T
authors: Jiang
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.|School of Medicine, Fudan University, Shanghai, China.
authors: Lanting
authors: L
authors: Wang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China.|Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Heng
authors: H
authors: Mei
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.
authors: Heng
authors: H
authors: Lu
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, PR China.|Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Yu
authors: Y
authors: Hu
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.
authors: Zhiqing
authors: Z
authors: Pang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D008856:Microscopy, Fluorescence; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D017239:Paclitaxel / Q000008:administration & dosage; D010477:Perfusion; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta; D017239:Paclitaxel
keywords: imatinib mesylate; micelles; nanomedicine size; nanoparticles; tumor microenvironment