Abstract
The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) in cancer treatment has attracted much attention in recent years. However, developing highly efficient and targeted therapeutic nanoagents for amplifying PTT and PDT treatments remains challenging. In this work, we developed a novel photothermal and photodynamic therapeutic nanoplatform for treatment of cancer cells overexpressing integrin αvβ3 through the coating of polydopamine (PDA) on indocyanine green (ICG)-loaded laponite (LAP) and then further conjugating polyethylene glycol-arginine-glycine-aspartic acid (PEG-RGD) as targeted agents on the surface. The ICG/LAP–PDA–PEG–RGD (ILPR) nanoparticles (NPs) formed could load ICG with a high encapsulation efficiency of 94.1%, improve the photostability of loaded ICG dramatically via the protection of PDA and LAP, and display excellent colloidal stability and biocompatibility due to the PEGylation. Under near-infrared (NIR) laser irradiation, the ILPR NPs could exert enhanced photothermal conversion reproducibly and generate reactive oxygen species (ROS) efficiently. More importantly, in vitro experiments proved that ILPR NPs could specifically target cancer cells overexpressing integrin αvβ3, enhance cellular uptake due to RGD-mediated targeting, and exert improved photothermal and photodynamic killing efficiency against targeted cells under NIR laser irradiation. Therefore, ILPR may be used as effective therapeutic nanoagents with enhanced photothermal conversion performance and ROS generating ability for targeted PTT and PDT treatment of cancer cells with integrin αvβ3 overexpressed.
Highlights
Photothermal therapy (PTT) and photodynamic therapy (PDT) are emerging physical tumor treatments utilizing near infrared (NIR) light-absorbing agents which lead to thermal ablation of cancer cells or generate highly reactive oxygen species (ROS) via photosensitizer to ablate tumors [1,2]
Indocyanine green (ICG) was firstly loaded in LAP nanodisks in order to increase the stability of ICG in solution, and PDA were coated on the surface of ICG/LAP to provide additional photothermal conversion efficacy for the nanoplatform and protection for ICG, followed by the modification of RGD–polyethylene glycol (PEG) to improve its stability and target cancer cells overexpressing integrin αvβ3 (Scheme 1)
In comparison with the absorbance of free ICG, the red-shift and broader half-wild of the absorption peak of ICG/LAP is probably attributed to the loading and aggregation of ICG in LAP, which may be more favorable for the photothermal heating with the NIR laser at 808 nm
Summary
Photothermal therapy (PTT) and photodynamic therapy (PDT) are emerging physical tumor treatments utilizing near infrared (NIR) light-absorbing agents which lead to thermal ablation of cancer cells or generate highly reactive oxygen species (ROS) via photosensitizer to ablate tumors [1,2]. The application of ICG in tumor phototherapy is limited by its tendency to aggregate, rapid degradation in aqueous solution [19], poor photo-stability and non-specific binding to proteins [20] To overcome those limitations, various nanoparticle delivery systems have been developed to encapsulate ICG [21]. The encapsulation of ICG in LAP nanodisks and the coating of PDA on the surface may improve the stability of ICG, provide additional photothermal conversion efficacy, and facilitate the targeting modification of a nanoplatform. To the best of our knowledge, this is the first study on the synthesis of ILPR NPs as effective therapeutic agents for targeted PTT and PDT treatment of cancer cells with overexpressed integrin αvβ
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