Camptothecin-based prodrug nanomedicines for cancer therapy

Abstract

Camptothecin (CPT) is a cytotoxic alkaloid that attenuates the replication cancer cells via blocking DNA topoisomerase 1. Despite its encouraging and wide spectrum antitumour activity, its application is significantly restricted...

Unleashing the Potential of Camptothecin: Exploring Innovative Strategies for Structural Modification and Therapeutic Advancements

“…Moreover, multifunctionality is a current focus, with research dedicated to constructing nanoscale delivery systems that integrate capabilities like controlled release, stimulus-responsive release, fluorescence imaging, and phototherapy, thereby offering a more holistic therapeutic approach. 108 4.2.1. Enhanced Permeability and Retention Effect.…”

“…These systems can also achieve controlled drug release that maintains optimal drug concentrations over an extended period, thereby prolonging the circulation time of drugs, and stimuli-responsive release triggered by the tumor microenvironment further reduces off-target effects. Moreover, multifunctionality is a current focus, with research dedicated to constructing nanoscale delivery systems that integrate capabilities like controlled release, stimulus-responsive release, fluorescence imaging, and phototherapy, thereby offering a more holistic therapeutic approach …”

“…The EPR effect varies among human tumors and sometimes shows poor vascular permeability, making it less reliable for effective drug delivery. Furthermore, drug accumulation depends largely on factors like circulation time and random extravasation into the tumor tissue in these systems, rather than targeted intracellular delivery, which can lead to inconsistent therapeutic outcomes, reduced bioavailability, and unintended off-target effects. , Given these limitations, active targeting systems have emerged by incorporating tumor-specific ligands like antibodies, peptides, and small molecules that bind to overexpressed receptors on cancer cells, allowing for receptor-mediated endocytosis, thereby increasing cell-specific internalization and intracellular uptake, which not only provides greater control over drug delivery but also offers the potential for reduced side effects, representing an important advancement over EPR-based passive targeting.…”

Camptothecin-loaded supramolecular nanodelivery system based on amphiphilic calix[4]arene for targeted tumor therapy

“…Many clinical studies have shown that CPT and its derivatives can effectively inhibit a wide spectrum of human cancers, such as ovarian, bladder, colon, gastric, liver, leukemia, and breast cancers. 1–8 The structure–activity relationship indicated that the lactone ring in the structure of CPT significantly contributes to its anticancer activity. However, this could be broken into an inactive open loop through hydrolysis under physiological conditions.…”