Cancer Cell‐Specific Fluorescent Prodrug Delivery Platforms

Abstract

Targeting cancer cells with high specificity is one of the most essential yet challenging goals of tumor therapy. Because different surface receptors, transporters, and integrins are overexpressed specifically on tumor cells, using these tumor cell-specific properties to improve drug targeting efficacy holds particular promise. Targeted fluorescent prodrugs not only improve intracellular accumulation and bioavailability but also report their own localization and activation through real-time changes in fluorescence. In this review, efforts are highlighted to develop innovative targeted fluorescent prodrugs that efficiently accumulate in tumor cells in different organs, including lung cancer, liver cancer, cervical cancer, breast cancer, glioma, and colorectal cancer. The latest progress and advances in chemical design and synthetic considerations in fluorescence prodrug conjugates and how their therapeutic efficacy and fluorescence can be activated by tumor-specific stimuli are reviewed. Additionally, novel perspectives are provided on strategies behind engineered nanoparticle platforms self-assembled from targeted fluorescence prodrugs, and how fluorescence readouts can be used to monitor the position and action of the nanoparticle-mediated delivery of therapeutic agents in preclinical models. Finally, future opportunities for fluorescent prodrug-based strategies and solutions to the challenges of accelerating clinical translation for the treatment of organ-specific tumors are proposed.

Biomaterial-Mediated Exogenous Facile Coating of Natural Killer Cells for Enhancing Anticancer Efficacy toward Hepatocellular Carcinoma

“…Therefore, to examine the binding efficacy of LBA on surface-modulated NK cells, we performed cancer recognition against both ASGPR-positive HepG2 and ASGPR-negative MDA-MB-231 cancer cells. As represented in Figure a, LBA-NK cells showed enhanced targeting and recognition abilities toward HepG2 liver cancer cells while those cocultured with MDA-MB-231 and normal fibroblasts did not show LBA-mediated binding (Figure b,c), confirming sufficient membrane-mediated effector/target interaction via LBA-ASGPR binding …”

“…As represented in Figure 5a, LBA-NK cells showed enhanced targeting and recognition abilities toward HepG2 liver cancer cells while those cocultured with MDA-MB-231 and normal fibroblasts did not show LBA-mediated binding (Figure 5b,c), confirming sufficient membrane-mediated effector/target interaction via LBA-ASGPR binding. 51 Biomaterial-mediated immune surveillance of NK cells directly depends on binding affinity between LBA presented on the surface-engineered NK cells and ASGPR expressed on the target cell surfaces. After successfully binding with target cancer cells and subsequent activation of NK cells, NK cells secrete cytotoxic granules and cytokines to facilitate cytotoxicity against tumor cells.…”

Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

“…CMC Measurement. 12 To investigate the self-assembly in nanoscale behavior of TPE-Lenalidomide in water, the critical micelle concentration (CMC) was measured by using pyrene as a fluorescent probe (Figure S7). The fluorescence intensities of the first (I 1 ) and third (I 3 ) bands of pyrene are sensitive to the surrounding medium.…”

“…Cancer remains as one of the most significant diseases that seriously threatens human health all over the world. − In order to effectively inhibit malignant tumor and prolong survival, varieties of drug delivery systems and polymer prodrugs have been developed. − However, most of them are restricted by their low drug loading capacity, and serious cumulative cytotoxicity. , By comparison, small-molecule prodrugs − have the advantage of high loading capacity and easy metabolism for cancer therapeutics. Typically, Yan et al developed an amphiphilic small-molecule prodrug by integrating a hydrophilic anticancer drug and a hydrophobic anticancer drug via a hydrolyzable ester linkage and proposed the concept of amphiphilic drug–drug conjugate (ADDC), which opens up a new way for self-delivery systems.…”

Stimuli-responsive biotin-anchored prodrug for the targeted delivery of anti-cancer agent NBDHEX with turn-on NIR fluorescence

“…14 Moreover, the incorporation of a stimuli-responsive turn-on fluorogenic unit would support non-invasive, convenient monitoring of drug delivery. 15 Therefore, in the present study, we have developed a biothiol-activatable turn-on NIR fluorogenic and biotin-anchored prodrug RK-296 of NBDHEX for the targeted delivery of NBDHEX to cancer microenvironments with concomitant turn-on NIR fluorescence (Fig. 1).…”