Near-Infrared Laser-Triggered In Situ Dimorphic Transformation of BF₂-Azadipyrromethene Nanoaggregates for Enhanced Solid Tumor Penetration

Abstract

The shape of a drug delivery system impacts its in vivo behavior such as circulation time, accumulation, and penetration. Considering the advantages of functional dyes in bioapplications, we synthesize a class of nanoaggregates based on BF 2 -azadipyrromethene (aza-BODIPY) dyes, which can realize long blood circulation and deep tumor penetration simultaneously in vivo through morphological transformation modulated by a nearinfrared (NIR) laser. First, when the temperature increases, the wormlike nanofibers of the aza-BODIPY-1 aggregate, possessing a long blood circulation time, can be transformed into spherical nanoparticles, which are conducive to increasing the penetration in the solid tumor. Second, without any postmodification, the nanofibers exhibit an outstandingly narrow absorption band in the NIR spectral range, so that they possess ideal photothermal properties. Through 655 nm laser irradiation, the intrinsic photothermal effect causes a local temperature increase to ∼48 °C, realizing the transformation of 1-NFs to 1-NPs. Third, the morphological transformation is real-time detected by photoacoustic (PA) imaging. By monitoring the change of the PA signal at a specific wavelength, the in vivo deformation process of nanomaterials can be traced. Consequently, the in situ morphology transformation of aza-BODIPY-based nanomaterials can simultaneously realize long blood circulation and deep penetration, resulting in the enhanced antitumor outcome.

Applications of Surface Modification Technologies in Nanomedicine for Deep Tumor Penetration

“…synthesized a class of nanoaggregates based on BF2‐azadipyrromethene (aza‐BODIPY) dyes that could deform between wormlike nanofibrous and spherical nanoparticles under a NIR laser. [ 78 ] Wormlike nanofibrous aggregates were beneficial to achieve long blood circulation times, while spherical nanoparticles were beneficial for tumor penetration. An et al.…”

Self‐Assembled Nanoparticles as Cancer Therapeutic Agents

“…brought the BF 2 ‐azadipyrromethene (Aza‐BODIPY) dyes and TEG together to get a self‐assembled nanosystem, possessing two nanostructures of nanofiber and nanoparticles. [ 13a ] The nanofiber possesses great photothermal ability and could be transformed into nanoparticles with the temperature raising and through monitoring different photoacoustic signals, the morphology transformation could be detected. Zhang and co‐workers reported a dextran (DEX) polysaccharide‐based nanodrug that can self‐assemble into stable nanoscale spherical micelles in water.…”

“…The nanoparticles have good intratumoral permeability and prolonged blood circulation duration and can release DOX, an anticancer drug doxorubicin (DOX), in tumor acidic environment, showing excellent therapeutic efficacy ( Figure A). [ 13c ] Jin et al. combined phospholipid long chain analogs and phthalocyanines and the obtained molecules could self‐assemble into nanoparticles, finally enhancing the PDT.…”

“…[ 10c,11 ] Through molecular self‐assembly, one drug can interact and aggregate individually or together with other drugs to form a stable and ordered nanostructure (such as nanosphere, nanofiber, nanorod), which has unique physicochemical properties different from the original agents or simple mixed original agents and the formed nanoparticles usually hold excellent pharmacological properties in cancer treatment. [ 12 ] SANPs as therapeutic agents may be a novel and promising paradigm for highly efficient cancer therapy due to the following attractions: [ 13 ] i) Benefiting from the noncovalent forces, the preparation of nanoparticles may be facile and green, it is suitable for large‐scale fabrication. ii) Compared with the free form, the obtained SANPs possess enhanced treatment efficiency due to its great properties including better biocompatibility, passive targeting, overcoming multidrug resistance, high drug loading rates, and lower side effects.…”

An ultra-stable bio-inspired bacteriochlorin analogue for hypoxia-tolerant photodynamic therapy

“…To address this issue, some strategies such as two-photon excitation (TPE) technique 4,5 and upconversion nanoparticles (UCNPs) 6,7 had been introduced for the therapy of deep tumors, but the complex equipment and the low conversion efficiency will bring about new problems for the clinic application 8,9 . Thus, PSs with strong NIR (700-1000 nm) absorption, which display deeper tissue penetration and minimized photodamage, have attracted intense research efforts for eradicating tumor in deep site [10][11][12] . Moreover, the PDT efficacy is also greatly suffered from the hypoxia environment of solid tumors, since the conventional PSs consume oxygen to produce reactive oxygen species (ROS) for inhibiting tumor growth (type II mechanism).…”