title: Conjugated polymer and drug co-encapsulated nanoparticles for chemo- and photo-thermal combination therapy with two-photon regulated fast drug release.
abstract: The spatial-temporal synchronization of photothermal therapy and chemotherapy is highly desirable for an efficient cancer treatment with synergistic effect. Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained nanoparticles (NPs) exhibit good monodispersity and excellent stability, which can efficiently convert laser energy into thermal energy for photothermal therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2-naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR two-photon laser irradiation, which leads to fast drug release. Furthermore, the surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD) tripeptide significantly enhances the accumulation of the NPs within integrin αvβ3 overexpressed cancer cells. The half-maximal inhibitory concentration (IC50) of the combination therapy is 13.7 μg mL(-1), while the IC50 for chemotherapy and photothermal therapy alone is 147.8 μg mL(-1) and 36.2 μg mL(-1), respectively. The combination index (C.I.) is 0.48 (<1), which indicates the synergistic effect for chemotherapy and PTT. These findings provide an excellent NIR laser regulated nanoplatform for combined cancer treatment with synergistic effect due to the synchronous chemo- and photo-thermal therapy.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585, Singapore. cheliub@nus.edu.sg.
authors.forename: Youyong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Zuyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Pingqiang
authors.initials: P
authors.lastname: Cai
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Lun-De
authors.initials: LD
authors.lastname: Liao
authors.forename: Minghui
authors.initials: M
authors.lastname: Hong
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.forename: Nitish
authors.initials: N
authors.lastname: Thakor
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D006979:Hyperthermia, Induced; D020128:Inhibitory Concentration 50; D039302:Integrin alphaVbeta3 / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D007834:Lasers; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology; D009285:Naphthoquinones / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D009842:Oligopeptides / Q000737:chemistry; D010778:Photochemotherapy; D017785:Photons; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D009285:Naphthoquinones; D009842:Oligopeptides; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin