title: Drug-induced co-assembly of albumin/catalase as smart nano-theranostics for deep intra-tumoral penetration, hypoxia relieve, and synergistic combination therapy.
abstract: The abnormal tumor microenvironment (TME) featured with hypoxia, acidosis, dense extracellular matrix and increased tumor interstitial fluid pressure is closely related with the resistance of tumors to various therapies. Herein, a unique type of biocompatible nanoscale delivery system is fabricated by utilizing a chemotherapeutic drug, paclitaxel (PTX), to induce co-assembly of catalase and human serum albumin (HSA), the latter of which is pre-modified with chlorine e6 (Ce6), forming smart multifunctional HSA-Ce6-Cat-PTX nanoparticles via a rather simple one-step method. Upon intravenous injection, HSA-Ce6-Cat-PTX nanoparticles show high tumor accumulation and efficient intra-tumoral diffusion, likely owning to their changeable sizes that can maintain large initial sizes (~100nm) during blood circulation and transform into small protein-drug complexes (<20nm) within the tumor. Meanwhile, catalase within those nanoparticles could trigger decomposition of endogenic TME H2O2to generate oxygen in-situ so as to relieve tumor hypoxia. This effect together with PTX-induced intra-tumoral perfusion enhancement is able to dramatically modulate TME to favor the anti-tumor effect in the combined photodynamic/chemotherapy with HSA-Ce6-Cat-PTX. Thus, our work presents a simple drug-induced self-assembly strategy to fabricate enzyme-loaded therapeutic albumin nanoparticles for synergistic cancer combination therapy.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Song
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Song
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China. Electronic address: zliu@suda.edu.cn.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002374:Catalase / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D003131:Combined Modality Therapy; D005260:Female; D006861:Hydrogen Peroxide / Q000737:chemistry; D000860:Hypoxia; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011166:Porphyrins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000068936:Theranostic Nanomedicine; D059016:Tumor Microenvironment
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D012709:Serum Albumin; C062985:phytochlorin; D006861:Hydrogen Peroxide; D002374:Catalase; D017239:Paclitaxel
keywords: Albumin; Combination therapy; Deep penetration; Hypoxia relieve; Self-assembly