Iron(III) Coordinated Theranostic Polyprodrug with Sequential Receptor-Mitochondria Dual Targeting and T₁-Weighted Magnetic Resonance Imaging Potency for Effective and Precise Chemotherapy

Abstract

The sequential cancer cell receptor and mitochondria dual-targeting single delivery agent deliver chemotherapeutic drug effectively and precisely at the targeted site has become a promising strategy to enhance the drug efficacy and suppressions of cancer cell drug resistance prominence. Herein, required specialty molecules like a chemotherapeutic drug [camptothecin (CPT)], mitochondriotropic segment (triphenyl phosphonium cation) receptor targeting ligand (biotin), and magnetic resonance imaging (MRI)-contrast agent (iron-complex) were tethered to the polyprodrug, CP TP PG BN Fe, using the ring-opening metathesis polymerization technique for potential chemotherapy and simultaneous MRI-based diagnosis. This amphiphilic polyprodrug spontaneously aggregated into nanospheres and exhibited remarkable T 1 -weighted MRI proficiency. Detail in vitro cellular studies revealed unambiguous mitochondrial delivery of CPT, which eventually enhanced the chemotherapeutic efficacy of CP TP PG BN Fe. Therefore, MRI-tracking, receptor-mitochondria dual targeting, theranostic polyprodrug, and CP TP PG BN Fe opened the way for effective and precise chemotherapy, which would have the attractive potential for diagnosis and decisive dose determination in clinical implications.

Structural Engineering of l-Aspartic Amphiphilic Polyesters for Enzyme-Responsive Drug Delivery and Bioimaging in Cancer Cells

“…Polymers are emerging as indispensable components in biomedical applications, and they have become an integral part of drug delivery systems, − gene delivery vehicles, tissue engineering scaffolds, , and antimicrobial agents. , Synthetic polymers gained significant importance because of their tunable properties, including biocompatibility, biodegradability, and versatility in molecular design, which made them highly attractive for addressing diverse biomedical challenges. − Among the myriad classes of polymers, biodegradable variants hold particular significance, offering controlled degradation that aligns with the dynamic needs of biological systems. − These polymers not only mitigate concerns related to long-term accumulation and toxicity but also facilitate the controlled release of therapeutic agents, thereby enhancing efficacy and minimizing adverse effects. − Within the domain of biodegradable polymers, those derived from natural resources hold immense promise; notably, the polymers synthesized from l -amino acids via ring-opening polymerization (ROP) have garnered considerable attention owing to their inherent biocompatibility and structural resemblance to biological macromolecules. − This includes the development of synthetic amphiphilic polypeptides mimicking the natural-protein-type self-assemblies under physiological conditions . To address the limitation in the biodegradation aspects and broaden the scope of biomedical applications of l -amino acid bioresources, alternative nonpeptide analogues such as poly(ester amides), − polycarbonates, poly(ester urea urethanes), poly(disulfide urethanes), and poly(acetal urethanes) have been explored.…”