In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics

Abstract

The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

Functional Peptide Nanofibers with Unique Tumor Targeting and Enzyme‐Induced Local Retention Properties

“…Importantly, our PET imaging studies showed that GSH-NFP could eventually saturate the entire tumor over time. Unlike other stimuli-responsive organic and inorganic nanocarriers designed to aggregate at the tumor microenvironment to improve the retention on site and play the role of drug-delivery depots, [39] our NFPs can structurally evolve into more than ten times larger interfibril networks via tumor-associated protease activation to prolong local retention for weeks. Overall, the unique combination of tumor uptake, penetration, infiltration, residing, and retention properties confer great potential on advanced GSH-NFP as a carrier of chemotherapeutic agents.…”

CCCCC pentadentate chelates with planar Möbius aromaticity and unique properties

“…To monitor the PTT efficiency, the tumor volumes were measured every other day for 2 weeks ( 39 , 40 ). The following equation was used to monitor the volume change of tumors: tumor volume = length × width 2 /2.…”

Inorganic Nanocarriers Overcoming Multidrug Resistance for Cancer Theranostics

“…Moreover, inorganic nanocarriers could provide multifunctional platforms for cancer treatment, such as hyperthermia therapy,67, 68 which demonstrated potential to reverse MDR in cancers by combination with chemotherapy 69. More importantly, these inorganic nanocarriers could also provide molecular imaging function, which could help monitoring drug delivery processes and therapeutic outcomes, leading to improved treatment efficacy, especially for treating MDR cancers 70, 71…”