Spermine‐Responsive Intracellular Self‐Aggregation of Gold Nanocages for Enhanced Chemotherapy and Photothermal Therapy of Breast Cancer

Abstract

Improving the precise accumulation and retention of nanomedicines in tumor cells is one of the keys to effective therapy of tumors. Herein, supramolecular peptides capped Au nanocages (AuNCs) that may self‐aggregate into micron‐sized clusters intracellularly in response to spermine (SPM), leading to specific accumulation and retention of AuNCs in SPM‐overexpressed tumor cells, are developed. In this design, polydopamine (PDA) is in situ coated on the surface of AuNCs with doxorubicin (DOX) encapsulated. A small peptide, Phe‐Phe‐Val‐Leu‐Lys (FFVLK), is conjugated with PDA via esterification, and cucurbit[7]uril (CB[7]) is threaded onto the N‐terminal Phe via host‐guest interactions. Once the supramolecular peptide (CB[7]‐FFVLK) capped AuNCs are internalized in SPM‐overexpressed breast cancer cells, CB[7] can be competitively removed from FFVLK by SPM, due to the much higher binding affinity between CB[7] and SPM than that between CB[7] and Phe, leading to exposure of free FFVLK, which can subsequently self‐assemble and induce the aggregation of AuNCs to micron‐sized clusters, resulting in the significantly enhanced accumulation and retention of DOX‐loaded AuNCs in tumor cells. Under NIR laser irradiation, the enhanced photothermal conversion of AuNCs aggregates, together with photothermia‐induced release of DOX leads to synergistic photothermal therapy and chemotherapy against breast cancer.

Fluorophore-based host–guest assembly complexes for imaging and therapy

“…46 Most importantly, owing to the considerable biocompatibility and inherent inclusion of macrocycles, strategies based on host-guest assembly have been widely used in recent years for constructing drug delivery systems, 66,67 synthesizing antimicrobial materials, 44,[68][69][70] and designing biomedical reagents. [71][72][73][74] This paper will focus on the development and biological applications of host-guest strategies in fluorophore-based bioimaging and therapeutic reagents and their potential challenges and prospects.…”

Host-guest assemblies for improved photothermal cancer therapy

“…In other cases, the unique microenvironment of tumor site [48][49][50] can drive the reorganization of host-guest assembly, which will then affect the photothermal conversion efficiency of host-guest assembly-based agents. Spermine, which overexpresses in some types of tumors (e.g., breast cancer), was employed as external stimuli for the photothermal performance enhancement of host-guest assemblies.…”

Phenylboronic Acid‐Modified Near‐Infrared Region II Excitation Donor–Acceptor–Donor Molecule for 2‐Deoxy‐d‐Glucose Improved Starvation/Chemo/Photothermal Combination Therapy

“…[ 7 ] To cope with these challenges, the association of chemotherapy with photothermal therapy (PTT) emerged as a therapeutic paradigm by coloading drugs and photothermal agents into drugv delivery systems. [ 8–10 ]…”

“…[7] To cope with these challenges, the association of chemotherapy with photothermal therapy (PTT) emerged as a therapeutic paradigm by coloading drugs and photothermal agents into drugv delivery systems. [8][9][10] Second near-infrared window fluorescence (NIR-II FL; 1000-1700 nm) imaging of small donor-acceptor-donor (D-A-D) organic molecules is one class of photothermal transfer agents has been reported for chemo/PTT combination therapy owing to the adjustable optical-physics performance and favorable biocompatibility. [11,12] Under light irradiation, D-A-D small molecules can achieve local hyperthermia and NIR-II FL simultaneously, thereby realizing tumor apoptosis and diagnosis.…”