Redox-Activated Light-Up Nanomicelle for Precise Imaging-Guided Cancer Therapy and Real-Time Pharmacokinetic Monitoring

Abstract

Simultaneous tumor imaging, therapy, and pharmacokinetic monitoring can offer a safe and effective strategy for cancer therapy. This work describes the design of a fluorescence light-up nanomicelle that can afford precise imaging-guided drug delivery and pharmacokinetic monitoring in a real-time fashion for cancer chemotherapy. The nanomicelle, which contains a boron dipyrromethene based fluorescent probe as the hydrophobic core and a redox-triggered detachable poly(ethylene glycol) (PEG) shell, can accumulate at the tumor site via enhanced permeation and retention effect. The PEG detachment induced by tumoral and intracellular glutathione can destabilize the nanomicelle, leading to fluorescence light up and simultaneous drug release. Importantly, the fluorescence intensities generated by the nanomicelles in different organs are well-correlated with released drug concentrations in both temporal and spatial manners, suggesting its precise role for imaging-guided drug delivery and pharmacokinetic monitoring in vivo. The tumor growth can be effectively inhibited by the docetaxel-loaded nanomicelle formulation, and the nanomicelles are monitored to be excreted via hepatobiliary routes. This nanomicelle for precise imaging-guided chemotherapy provides a safe and robust theranostic strategy for the evaluation of cancer nanomedicine.

A Cooperative Dimensional Strategy for Enhanced Nucleus‐Targeted Delivery of Anticancer Drugs

“…These results suggest that the PSPD/P 123 ‐Dex micelles could efficiently target the nucleus and facilitate efficient nuclear penetration. To evaluate the penetration capability of the DOX‐loaded micelles, HeLa cells were used to construct 3D tumor spheroids to mimic the morphology and microenvironment of solid tumors ( Figure ) . The fluorescence signal of PPD/DOX micelles was primarily distributed on the periphery of the tumor spheroids, implying the poor ability of PPD/DOX micelles to penetrate into deep tumor tissues.…”

Integration of Indocyanine Green Analogs as Near‐Infrared Fluorescent Carrier for Precise Imaging‐Guided Gene Delivery

“…Ideally a tracer should allow for an investigation of biodistribution as well as intracellular localization at the same time. In the past decade, theranostic concept provides a promising strategy for simultaneous drug or gene delivery and molecular imaging in a single system and gives a capability to visualize and quantify the pharmacokinetic processes of cellular and molecular therapies (adsorption, distribution, metabolism, and excretion) at both cellular and tissue levels in a real‐time fashion . Particularly, imaging‐guided drug delivery can monitor the path of drugs in vivo, evaluate the efficiency of tumor‐targeted delivery, and further provide information regarding pharmacokinetics of the treatment …”

“…Therefore, researchers attempted to rationally integrate the fluorescent probe as “main” portion of the carriers. Some amphiphilic drug delivery carriers that taking the advantage of strong hydrophobic properties of boron dipyrromethene (BODIPY) have developed . And platinated‐BODIPY molecules have been designed to combine chemical, photodynamic, and photothermal therapy together for tumor ablation, showing encouraging prospect.…”

From Supramolecular Vesicles to Micelles: Controllable Construction of Tumor‐Targeting Nanocarriers Based on Host–Guest Interaction between a Pillar[5]arene‐Based Prodrug and a RGD‐Sulfonate Guest

“…Over the past few decades, research concerning drug nanocarriers has been widely explored for anticancer drug delivery to increase the drug accumulation by means of passive accumulation via tumors' enhanced permeation and retention (EPR) effect . Although some therapeutic advantages have been demonstrated in different systems, the field of controlled drug delivery systems (DDSs) still faces two major challenges. One is the fabrication of morphology and size‐controllable DDSs with high drug‐loading capacity to facilitate the drug accumulation and reduce the carriers' systemic toxicity and extra burden for the patients.…”