Smart Peptide-Based Supramolecular Photodynamic Metallo-Nanodrugs Designed by Multicomponent Coordination Self-Assembly

Abstract

Supramolecular photosensitizer nanodrugs that combine the flexibility of supramolecular self-assembly and the advantage of spatiotemporal, controlled drug delivery are promising for dedicated, precise, noninvasive tumor therapy. However, integrating robust blood circulation and targeted burst release in a single photosensitizer nanodrug platform that can simultaneously improve the therapeutic performance and reduce side effects is challenging. Herein, we demonstrate a multicomponent coordination self-assembly strategy that is versatile and potent for the development of photodynamic nanodrugs. Inspired by the multicomponent self-organization of polypeptides, pigments, and metal ions in metalloproteins, smart metallo-nanodrugs are constructed based on the combination and cooperation of multiple coordination, hydrophobic, and electrostatic noncovalent interactions among short peptides, photosensitizers, and metal ions. The resulting metallo-nanodrugs have uniform sizes, well-defined nanosphere structures, and high loading capacities. Most importantly, multicomponent assembled nanodrugs have robust colloidal stability and ultrasensitive responses to pH and redox stimuli. These properties prolong blood circulation, increase tumor accumulation, and enhance the photodynamic tumor therapeutic efficacy. This study offers a new strategy to harness robust, smart metallo-nanodrugs with integrated flexibility and multifunction to enhance tumor-specific delivery and therapeutic effects, highlighting opportunities to develop next-generation, smart photosensitizing nanomedicines.

Amino Acid Coordination Driven Self‐Assembly for Enhancing both the Biological Stability and Tumor Accumulation of Curcumin

“…TheU V/Vis absorption spectra of the B-Cur NPs and S-Cur NPs were nearly identical, with an absorption maximum at 430 nm assigned to the p-p*t ransition of curcumin and as houlder at 453 nm assigned to the charge transfer between curcumin and Zn 2+ (see Figure S3). In the absence of curcumin, the coordination-driven self-assembly of Fmoc-H formed Fmoc-H-Zn 2+ nanoparticles (see Figure S6), [19] which had an Fmoc-H:Zn 2+ molar ratio of approximately 2:1. Thec oordination interaction was also confirmed by Fourier transform infrared (FTIR) spectroscopy (see Figure S4) and 1 HNMR spectroscopy (see Figure S5).…”

Multistage Delivery Nanoparticle Facilitates Efficient CRISPR/dCas9 Activation and Tumor Growth Suppression In Vivo

“…The successful coating was confirmed with TEM and DLS measurements, leading to the increase in particle size to 205 ± 10.2 nm (Figure 2c) and the decrease in zeta potential to −12.5 ± 1.6 mV ( Figure S6, Supporting Information). [19] More importantly, acidic environment (pH = 6.5) triggered the breaking of the DMMA groups apart from mPEG 113 -b-PLys 100 / DMMA, which was first confirmed by monitoring the shiftiness of the characteristic peak attributed to the hydrogen adjacent to amide bond/amino group using 1 H NMR ( Figure 2a). As a result, MDNP exhibited enhanced stability in PBS containing 10% fetal bovine serum (FBS) ( Figure S8, Supporting Information), suggesting the potential to evade the immune clearance during circulation in blood.…”

Dual Stimuli‐Responsive Controlled Release Nanocarrier for Multidrug Resistance Cancer Therapy

“…In recent years, nanocarriers have been intensively investigated for cancer therapeutics . To date, many mechanisms have been proposed to regulate the time, rate and location of the drugs .…”