Abstract
How to actively target tumor sites manipulating the controllable release of the encapsulated anticancer drugs and photosensitizers for synergistic anticancer therapy remains a big challenge. In this study, a cancer cell-targeted, near-infrared (NIR) light-triggered and anticancer drug loaded liposome system (LPs) was developed for synergistic cancer therapy. Photosensitizer indocyanine green (ICG) and chemotherapy drug Curcumin (CUR) were coencapsulated into the liposomes, followed by the surface conjugation of GE11 peptide for epidermal growth factor receptor (EGFR) targeting on the cancer cell surface. Strictly controlled by NIR light, GE11 peptide modified and CUR/ICG-loaded LPs (GE11-CUR/ICG-LPs) could introduce hyperthermia in EGFR overexpressed A549 cancer cells for photothermal therapy, which could also trigger the increased release of CUR for enhanced cancer cell inhibition. GE11-CUR/ICG-LPs synergized photochemotherapy could induce reactive oxygen species (ROS) generation and cytoskeleton disruption to activate stronger apoptotic signaling events than the photothermal therapy or chemotherapy alone by regulating Bax/Bcl-2 and PI3K/AKT pathways. This EGFR-targeted drug-delivery nanosystem with NIR sensitivity may potentially serve in more effective anticancer therapeutics with reduced off-target effects.
Highlights
As one of the leading causes of death, cancer is accounting for millions of deaths annually worldwide [1]
Photosensitizer indocyanine green (ICG) and chemotherapeutic agent CUR were coencapsulated into liposomes through film hydration, followed by conjugation with GE11 peptides for epidermal growth factor receptor (EGFR)-positive A549 cancer cell targeting
Dynamic light scattering (DLS) measurements showed that LPs were ∼220 nm spherical particles with homogeneous distribution (Figure 1(b)), which was suitable for passive targeting of the tumor through the EPR effect [35]
Summary
As one of the leading causes of death, cancer is accounting for millions of deaths annually worldwide [1]. Despite the rapid advances in recent therapy techniques, chemotherapy is still the principal cancer treatment approach in the clinic. The low cancer targeting effect, low bioavailability, poor aqueous solubility, and fast metabolism still restrict the anticancer effects of CUR, which further hinders its clinical use. Us, how to enhance the anticancer effects of CUR by some novel strategies remains the most urgent challenge for its further clinical application. Owing to the fascinating physical and chemical properties, liposomes (LPs) have been extensively used to improve the solubility and bioavailability of CUR, attracting substantial attention in the past decades [11]. Poly(ethylene glycol) polymer (PEG) modification enables liposomes to effectively
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