Near-Infrared Fluorescent Dye-Decorated Nanocages to Form Grenade-like Nanoparticles with Dual Control Release for Photothermal Theranostics and Chemotherapy

Abstract

Recently, nanoparticles (NPs) have been widely investigated for delivery of anticancer drugs. Here, a dual control drug-release modality was developed that uses naturally occurring protein apoferritin loaded with doxorubicin (DOX) and ADS-780 near-infrared (NIR) fluorescent dye-decorated NPs (ADNIR NPs). ADNIR NPs act as a grenade to detonate the targeted tumor site following laser irradiation (photothermal therapy, PTT) and explode into cluster warheads (apoferritin-loaded DOX nanocages, AF-DOX NCs) that further destroy the tumor cells (chemotherapy). Light was shown to disrupt the grenade-like structure of NPs to release AF-DOX NCs as well as DOX from NCs in low-pH intercellular environments. In vitro and in vivo studies showed that the structure of AF-DOX NCs was disassembled to release DOX, which then killed the cancer cells in organelles with acidic environments. In vivo studies showed that the ADNIR NP-decorated with NIR dye facilitated tracking of the accumulated NPs at the tumor site using an IVIS imaging system. Overall, targeted ADNIR NPs with dual-release mechanisms were developed for use in photothermal theranostic and chemotherapy. This modality has high potential for application in cancer treatment and clinical translation for drug delivery and imaging.

Recent Advances in Nanomaterials-Based Chemo-Photothermal Combination Therapy for Improving Cancer Treatment

“…Encouragingly, combined chemo-photothermal therapy realized successful suppression of MCF-7 and DOX-resistant MCF-7/ADR tumor growth as well as prevention of tumor recurrence in vivo . Similarly, many other attempts have been made to co-encapsulate various NIR dyes and drugs in different kinds of nano-carriers like liposomes (Li et al, 2015; Feng et al, 2016; Yan et al, 2016; Gao et al, 2018; Mu et al, 2019), polymeric nanoparticles (Su et al, 2015; Zhu et al, 2015; Chen Y. et al, 2017; Wang et al, 2017; Deng et al, 2018; He H. Z. et al, 2018; Yao et al, 2018; Tan et al, 2019; Zhang et al, 2019), protein nanoparticles (Chen et al, 2015; Lin and Shieh, 2018; Gao et al, 2019; Pei et al, 2019), and cell membranes (Sun et al, 2015; Li X. et al, 2018; Wan et al, 2018; Zhang N. et al, 2018; Ye et al, 2019). For example, Liu et al developed “Abraxane-like” nanodrug through self-assembly of human serum albumin (HSA), paclitaxel (PTX), and ICG in a simple mixing manner (Chen et al, 2015).…”

Bioengineered Ferritin Nanocarriers for Cancer Therapy

“…Dual controlled-release nanoparticle systems with external light-heat effect and intracellular pH-triggered release were developed for combination therapy. Lin et al [60] developed grenade-like nanoparticles with an average particle size of 60.1 nm by linking apoferritin-loaded DOX nanocages (AF-DOX NCs) with ADS-780 NIR fluorescent dye via hydrophobic interactions and electrostatic (Figure 7). After intravenous injection of grenade-like nanoparticles into mice, they passively accumulated at the tumor site due to the EPR effect.…”