A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy

Abstract

Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (1O2) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt3)2Pt(OTf)2 as the building block to improve the 1O2 QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics.

A self-assembled Ru–Pt metallacage as a lysosome-targeting photosensitizer for 2-photon photodynamic therapy

“…building blocks and Lewis-basic organic donor building blocks via coordination interactions, is a modular approach for the synthesis of discrete supramolecular coordination complexes (SCCs) with high structural and functional complexity (34)(35)(36)(37). By judicious selection of the molecular building blocks, the shapes, geometries, and biological properties of the SCCs can be precisely modulated to promote biomedical applications, such as anticancer activity (38)(39)(40)(41)(42), drug delivery (43)(44)(45)(46), bioimaging (47,48), and biorecognition (49)(50)(51). Self-assembled metallacycles have shown potential as photosensitizers for catalysis as well as PDT for cancer therapy and bacterial inactivation (39,40,(52)(53)(54).…”

“…By judicious selection of the molecular building blocks, the shapes, geometries, and biological properties of the SCCs can be precisely modulated to promote biomedical applications, such as anticancer activity (38)(39)(40)(41)(42), drug delivery (43)(44)(45)(46), bioimaging (47,48), and biorecognition (49)(50)(51). Self-assembled metallacycles have shown potential as photosensitizers for catalysis as well as PDT for cancer therapy and bacterial inactivation (39,40,(52)(53)(54). We envisioned that SCCs with a high level of structural complexity, such as metallacages, could provide favorable photophysical and biological properties over their 2D counterparts due to their 3D structure and high number of functional moieties within the same ensemble.…”

<p>Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer</p>

“…In past decades, the inherent limitations of traditional cancer therapy have led to the development and application of various nanotechnologies to treat cancer more effectively and safely. 13,14 The increasing interest in nanotechnology for cancer is due to its unique and attractive features, such as its utility for drug delivery, diagnosis, imaging, and synthetic vaccine development, as well as the inherent therapeutic properties of some nanomaterials. [15][16][17] To precisely control the release of drug at the tumor site and to meet requirements for increased anti-tumor effect and reduced damage to normal tissues, research has made great contributions in the area of stimuli-responsive release of materials (for example, pH, redox state, and enzymes).…”

Novel T7-modified pH-responsive targeted nanosystem for co-delivery of docetaxel and curcumin in the treatment of esophageal cancer

“…In past decades, the inherent limitations of traditional cancer therapy have led to the development and application of various nanotechnologies to treat cancer more effectively and safely [13,14]. The increasing interest in nanotechnology for cancer is due to its unique and attractive features, such as its utility for drug delivery, diagnosis, imaging and synthetic vaccine development, as well as the inherent therapeutic properties of some nanomaterials [15][16][17].…”