ACPI Conjugated Gold Nanorods as Nanoplatform for Dual Image Guided Activatable Photodynamic and Photothermal Combined Therapy In Vivo.

The nanoplatform GNR-ACPP-PpIX (designated as GNR-ACPI) is designed for dual image guided combined activatable photodynamic therapy (PDT) and photothermal therapy (PTT). In GNR-ACPI, gold nanorods (GNRs) are modified with a protoporphyrin (PpIX, a PDT agent) conjugated activatable cell penetrating peptide (ACPP), which consists of the matrix metalloproteinases-2 (MMP-2) sensitive peptide sequence GPLGLAG. First, the photoactivity of PpIX is effectively quenched by GNRs due to the strong near infrared region light absorption of GNR and the special "U type" structure of ACPP induced close contact between PpIX and GNR. However, once arriving at the tumor site, the GPLGLAG sequence is hydrolyzed by the MMP-2 overexpressed by tumor cells, resulting in the release of the residual cell membrane penetrating peptide (CPP) attached PpIX (CPP-PpIX) with the recovery of photoactivity of PpIX. In addition, with the help of CPP, more efficient cellular uptake of PpIX by tumor cells can be achieved, which will greatly improve the PDT efficacy. Moreover, the GNR can also be utilized for photothermic imaging as well as PTT for tumors. It is found that the combination of PTT and PDT under the guidance of dual-mode imaging greatly enhances the antitumor effects, while possessing negligible systematic toxicity.