Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Abstract

Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer‐based nanocarriers allow to increase plasma half‐life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well‐defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm. This article provides an overview of the different approaches that have been developed to control intracellular delivery of polymer nanomedicines and discusses the different techniques that can be used to monitor these processes.

Nanoscopy for endosomal escape quantification

“…Whilst significant progress has been made on developing a rich formulation databank of NP for cytosolic delivery (16,17), our understanding of the physiochemical and biological requisites for achieving endosomal escape has loitered (20,(26)(27)(28)(29)(30)(31). Our grasp of these mechanisms is hampered by the limitations of the standard techniques used to localise and quantify them.…”

“…1). Endosomal entrapment thus represents one of the main bottlenecks in using NP systems for gene therapy (20,(26)(27)(28) and proteins or small molecular drugs for the treatment of a variety of diseases (20,(29)(30)(31).…”

Synthesis of Passerini‐3CR Polymers and Assembly into Cytocompatible Polymersomes

“…The images suggest that P1 polymersomes were dispersed throughout the cytosol, suggesting potential escape from intracellular compartments following internalization via endocytosis. [ 18 ] This is the most common cell entry route for nanomaterials with a size range of 100–200 nm, [ 19 ] which are usually engulfed in the cell membrane and, then, are transported by dynamic vesicles from the plasma membrane to the cytoplasm. [ 18 ] The ability of P1‐Cy5 polymersomes to penetrate through model tumor tissue was assessed using 3D spheroids of MDA‐MB‐231 cells treated for 16 h with 0.047 µ m of P1‐Cy5 polymersomes.…”

Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy

“… 8 , 9 To obtain higher resolution, ex vivo techniques such as fluorescence microscopy, scanning transmission X-ray microscopy (STXM), Raman microspectral imaging, electron microscopy (EM), or nanoscale secondary ion mass spectrometry (NanoSIMS) have proven useful. 10 − 12 However, these techniques vary in sensitivity, resolution, nanoparticle labeling requirements, cost, availability, and sample preparation needs. 13 Further, to fully understand the relationship between nanomaterials and their biological behavior using these techniques individually is problematic.…”