RGD-Modified Albumin Nanoconjugates for Targeted Delivery of a Porphyrin Photosensitizer
journal contributionposted on 12.07.2017, 00:00 by Fang Li, Yan Zhao, Chengqiong Mao, Yi Kong, Xin Ming
Advances in photodynamic therapy of cancer have been restrained by lack of cancer specificity and side effects to normal tissues. Molecularly targeted photodynamic therapy can achieve higher cancer specificity by combination of active cancer targeting and localized laser activation. We aimed to use albumin as a carrier to prepare targeted nanoconjugates that are selective to cancer cells and smaller than conventional nanoparticles for superior tumor penetration. IRDye 700DX (IR700), a porphyrin photosensitizer, was covalently conjugated to human serum albumin that was also linked with tumor-targeting RGD peptides. With multiple IR700 and RGD molecules in a single albumin molecule, the resultant nanoconjugates demonstrated monodispersed and uniform size distribution with a diameter of 10.9 nm. These targeted nanoconjugates showed 121-fold increase in cellular delivery of IR700 into TOV21G ovarian cancer cells compared to control nanoconjugates. Mechanistic studies revealed that the integrin specific cellular delivery was achieved through dynamin-mediated caveolae-dependent endocytosis pathways. They produced massive cell killing in TOV21G cells at low nanomolar concentrations upon light irradiation, while NIH/3T3 cells that do not express integrin αvβ3 were not affected. Because of their small size, targeted albumin nanoconjugates could penetrate tumor spheroids of SKOV-3 ovarian cancer cells and produced strong phototoxicity in this 3-D model. Owing to their cancer-specific delivery and small size, these targeted nanoconjugates may become an effective drug delivery system for enabling molecularly targeted photodynamic therapy of cancer.
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cancer specificitySKOVNIHcancer cellsRGD-Modified Albumin NanoconjugatesPorphyrin Photosensitizer Advancesintegrin α v β3tumor-targeting RGD peptidesIR 700dynamin-mediated caveolae-dependent endocytosis pathwaysalbuminnanoconjugatedrug delivery systemphotodynamic therapyIRDye 700 DX3- D modelTOV 21G cellsuniform size distribution