Tailoring Platinum(IV) Amphiphiles for Self-Targeting All-in-One Assemblies as Precise Multimodal Theranostic Nanomedicine

Abstract

Drug, targeting ligand, and imaging agent are the three essential components in a nanoparticle-based drug delivery system. However, tremendous batch-to-batch variation of composition and drug content typically accompany the current approaches of building these components together. Herein, we report the design of photoactivatable platinum(IV) (Pt(IV)) amphiphiles containing one or two hydrophilic lactose targeting ligands per hydrophobic Pt(IV) prodrug for an all-in-one precise nanomedicine. Self-assembly of these Pt(IV) amphiphiles results in either micelle or vesicle formation with a fixed Pt/targeting moiety ratio and a constantly high content of Pt. The micelles and vesicles are capable of hepatoma cell-targeting, fluorescence/Pt-based CT imaging and have shown effective anticancer efficacy under laser irradiation in vitro and in vivo. This photoactivatable, active self-targeting, and multimodal theranostic amphiphile strategy shows great potential in constructing precise nanomedicine.

Photoactivatable Protherapeutic Nanomedicine for Cancer

“…[ 15 ] In a recent work by Zhou and co‐workers, an all‐in‐one photoactivatable Pt(IV) amphiphile photo‐nanotheranostics were tailored with hydrophilic lactose as targeting ligands ( Figure a). [ 16 ] The lactose ligands were in the axial positions of Pt(IV)−azide. Through controlling the number of lactose ligands conjugated to the Pt(IV)−azide, the amphiphiles self‐assembled into either nanomicelles or nanovesicles.…”

Diazido platinum(iv) complexes for photoactivated anticancer chemotherapy

“…These nanoparticles displayed photocytotoxicity with liver cancer-targeting ability in vivo. The platinum distribution in mice was determined by fluorescence, CT and ICP-MS. 132 For surface tumours, such as non-melanoma skin cancer, topical medication is an ideal way for precise localisation. G 4 K + hydrogels are biocompatible polymers with flexibility and high water content that allow them to mimic natural tissues.…”

NIR‐Light‐Activated Combination Therapy with a Precise Ratio of Photosensitizer and Prodrug Using a Host–Guest Strategy

“…There are three popular strategies employed for the codelivery of PSs with prodrugs:i )the covalent conjugation of aPStoaprodrug, [24] ii)grafting the PS or drug with acarrier, and loading the other component as the cargo, [32] iii)coloading the two components within acarrier,such as polymers and inorganic porous nanoparticles. [33][34][35][36] Each of these strategies has its own disadvantages.T he main challenge is the difficulty in fine-tuning the ratio between PS and drug, because the ratio is largely related to chemical structure, functionalities,a nd performance.F or the fabrication of covalently conjugated prodrugs,t here are some drawbacks including complicated organic synthesis and purification process.F or the other two strategies,a chieving ap recise ratio between the two components is also difficult due to potential premature leakage during the preparation and transportation processes.The uncertainty arising from imprecise loading of therapeutic components may lead to alow or unpredictable therapeutic efficacy of the cancer treatment.On account of their intrinsic cavity and easy functionalization, macrocycles,i ncluding crown ethers, [37] cyclodextrins (CDs), [38][39][40] cucurbiturils, [41,42] calixarenes, [43] and pillararenes, [44] have been widely employed as drug carriers,e ncapsulating chemotherapeutic drugs as guests.T hrough the formation of supramolecular complexes,t he solubility of the drugs is enhanced, leading to al onger circulation time and [*] Dr.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.…”

“…There are three popular strategies employed for the codelivery of PSs with prodrugs:i )the covalent conjugation of aPStoaprodrug, [24] ii)grafting the PS or drug with acarrier, and loading the other component as the cargo, [32] iii)coloading the two components within acarrier,such as polymers and inorganic porous nanoparticles. [33][34][35][36] Each of these strategies has its own disadvantages.T he main challenge is the difficulty in fine-tuning the ratio between PS and drug, because the ratio is largely related to chemical structure, functionalities,a nd performance.F or the fabrication of covalently conjugated prodrugs,t here are some drawbacks including complicated organic synthesis and purification process.F or the other two strategies,a chieving ap recise ratio between the two components is also difficult due to potential premature leakage during the preparation and transportation processes.The uncertainty arising from imprecise loading of therapeutic components may lead to alow or unpredictable therapeutic efficacy of the cancer treatment.…”