Two‐Stage Size Decrease and Enhanced Photoacoustic Performance of Stimuli‐Responsive Polymer‐Gold Nanorod Assembly for Increased Tumor Penetration

Abstract

A promising theranostic platform for solid tumors would deliver and release anticancer nanomedicine effectively in tumor cells. However, diverse biological barriers, especially related to the tumor microenvironment, impede these theranostic agents from reaching the tumor cell. Herein, a sequential pH and reduction-responsive polymer and gold nanorod (AuNR) core-shell assembly to overcome these barriers via a two-stage size decrease and disassembly of the nano platform responding to the specified tumor microenvironment are reported. The tumor uptake of the hybrid nanoparticle (NP) is 14.2% ID g −1 , which is two and four times higher than the noneresponsive hybrid NPs and small AuNR@PEG, respectively. After tumor uptake of the hybrid NPs, the disassembled ultrasmall AuNRs coated with a polymer of polymerized reduction-responsive doxorubicin (DOX) prodrug monomers penetrate into the solid tumor and lead to localized DOX release in the tumor cell. A linear increase in photoacustic (PA) effects from the PA activating polymer on an AuNR cluster surface indicates a critical role of electromagnetic fields in the AuNR assembly, which is consistent with the theoretical calculation results. Furthermore, the hybrid NP can serve as a promising deep-tissue PA and surfaceenhanced Raman scattering imaging agent for real-time in vivo investigation of physiological behaviors and deep tumor penetrating nanotherapy effects.

Surfactant‐Stripped Micelles for NIR‐II Photoacoustic Imaging through 12 cm of Breast Tissue and Whole Human Breasts

“…Generally, advanced nanomaterials have excellent potential for PAI owing to strong near infrared (NIR) absorption and can be used not only for photoacoustic contrast imaging but also photothermal therapy. [8,9] Silver nanocrystals [10] and transition-metal chalcogenides [11] have been demonstrated as PAI agents. Methylene blue (667 nm) has been used in clinical studies to detect sentinel lymph nodes (SLN) in breast cancer to approximately 1-2 cm in depth.…”

An Ultrasound Activated Vesicle of Janus Au‐MnO Nanoparticles for Promoted Tumor Penetration and Sono‐Chemodynamic Therapy of Orthotopic Liver Cancer

“…Thed ual-responsive amphiphilic JNP@PEG/PPADT were then synthesized by anchoring the hydrophobic ROS-sensitive polymer PPADT-SH and hydrophilic PEG-SH onto the Au surface through covalent Au-S bond. [13,15] Thes ynthesis route and characterization of PPADT are shown in the Supporting Information, Figure S4, [16] which would be broken due to SDT-mediated ROSg eneration by the activated JNP vesicles.…”

“…[11] Thus,J anus nanoparticles (JNPs) with biphasic core geometry provides the ability to combine these two distinct functions in one NP. [12] Furthermore,t he relatively small size of JNPs can significantly improve their tissue penetration, [13] however, the accumulation of these small-sized NPs in tumor area decreases during circulation. It is very meaningful to design as timuli-responsive nanoplatform to integrate functional JNPs into one nanoagent by using self-assembly of surfacefunctionalized JNPs.T he tumor activated self-assembly/disassembly of the nanoagents provides the possibility to overcome the dilemma of penetration and accumulation.…”

Shell‐Isolated Plasmonic Nanostructures for Biosensing, Catalysis, and Advanced Nanoelectronics

“…Very recently, Liu et al. [ 79 ] fabricated a pH and reduction‐responsive polymer shell‐isolated plasmonic AuNRs nano‐assembly ( Figure a). Due to the strong electromagnetic field and plasmonic coupling, the agent showed greatly enhanced photothermal and photoacoustic (PA) imaging performances (Figure 9b–d).…”