PMID- 31380107 OWN - NLM STAT- MEDLINE DCOM- 20191127 LR - 20200309 IS - 2050-7518 (Electronic) IS - 2050-750X (Print) IS - 2050-750X (Linking) VI - 6 IP - 47 DP - 2018 Dec 21 TI - A polymer-free, biomimicry drug self-delivery system fabricated via a synergistic combination of bottom-up and top-down approaches. PG - 7842-7853 LID - 10.1039/C8TB01464G [doi] AB - Compared to conventional carrier-assistant drug delivery systems (DDSs), drug self-delivery systems (DSDSs) have advantages of unprecedented drug loading capacity, minimized carrier-related toxicity and ease of preparation. However, the colloidal stability and blood circulation time of DSDSs still need to be improved. Here we report on the development of a novel biomimicry drug self-delivery system by the integration of a top-down cell membrane complexing technique into our self-delivery multifunctional nano-platform made from bottom-up approach that contains 100% active pharmaceutical ingredients (API) of Pheophorbide A and Irinotecan conjugates (named PI). Compared to conventional cell membrane coated nanoparticles with polymer framework as core and relatively low drug loading, this system consisting of red blood cell membrane vesicles complexed PI (RBC-PI) is polymer-free with up to 50% API loading. RBC-PI exhibited 10 times higher area under curve in pharmacokinetic study and much lower macrophage uptake compared with the parent PI nanoparticles. RBC-PI retained the excellent chemophototherapeutic effects of the PI nanoparticles, but possessed superior anti-cancer efficacy with prolonged blood circulation, improved tumor delivery, and enhanced photothermal effects in animal models. This system represents a novel example of using cell membrane complexing technique for effective surface modification of DSDSs. This is also an innovative study to form a polymer-free cell membrane nanoparticle complexing with positive surface charged materials. This biomimicry DSDS takes advantages of the best features from both systems to make up for each other's shortcomings and posed all the critical features for an ideal drug delivery system. FAU - Xu, Xiaobao AU - Xu X AD - College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China. AD - Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA. AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. FAU - Yang, Gaomai AU - Yang G AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. FAU - Xue, Xiangdong AU - Xue X AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. FAU - Lu, Hongwei AU - Lu H AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. FAU - Wu, Hao AU - Wu H AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. FAU - Huang, Yee AU - Huang Y AD - Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang 310021, China. FAU - Jing, Di AU - Jing D AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. FAU - Xiao, Wenwu AU - Xiao W AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. FAU - Tian, Jingkui AU - Tian J AD - College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China. FAU - Yao, Wei AU - Yao W AD - Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA. FAU - Pan, Chong-Xian AU - Pan CX AD - Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA. FAU - Lin, Tzu-Yin AU - Lin TY AD - Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA. FAU - Li, Yuanpei AU - Li Y AD - Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA. LA - eng GR - P30 CA093373/CA/NCI NIH HHS/United States GR - R01 CA176803/CA/NCI NIH HHS/United States GR - R01 CA232845/CA/NCI NIH HHS/United States GR - I01 BX001784/BX/BLRD VA/United States GR - R01 HD086195/HD/NICHD NIH HHS/United States GR - I01 BX003840/BX/BLRD VA/United States GR - R01 CA199668/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181112 PL - England TA - J Mater Chem B JT - Journal of materials chemistry. B JID - 101598493 RN - 0 (Antineoplastic Agents) RN - 0 (Drug Carriers) RN - 0 (Photosensitizing Agents) RN - 1406-65-1 (Chlorophyll) RN - 7673326042 (Irinotecan) RN - IA2WNI2HO2 (pheophorbide a) SB - IM MH - Animals MH - Antineoplastic Agents/pharmacokinetics/*pharmacology MH - Cell Line, Tumor MH - Chlorophyll/*analogs & derivatives/pharmacokinetics/pharmacology/radiation effects MH - Drug Carriers/*chemistry/pharmacokinetics MH - Drug Liberation MH - Erythrocyte Membrane/*chemistry MH - Female MH - Humans MH - Irinotecan/pharmacokinetics/*pharmacology MH - Light MH - Mice, Nude MH - Nanoparticles/chemistry MH - Photochemotherapy/methods MH - Photosensitizing Agents/pharmacokinetics/*pharmacology/radiation effects MH - Rats, Sprague-Dawley PMC - PMC6676892 MID - NIHMS997310 COIS- Conflicts of interest All authors declare no conflict of interest. EDAT- 2019/08/06 06:00 MHDA- 2019/11/28 06:00 PMCR- 2019/12/21 CRDT- 2019/08/06 06:00 PHST- 2019/08/06 06:00 [entrez] PHST- 2019/08/06 06:00 [pubmed] PHST- 2019/11/28 06:00 [medline] PHST- 2019/12/21 00:00 [pmc-release] AID - 10.1039/C8TB01464G [doi] PST - ppublish SO - J Mater Chem B. 2018 Dec 21;6(47):7842-7853. doi: 10.1039/C8TB01464G. Epub 2018 Nov 12.