Photosensitive nanocarriers for specific delivery of cargo into cells

Abstract

Nanoencapsulation is a rapidly expanding technology to enclose cargo into inert material at the nanoscale size, which protects cargo from degradation, improves bioavailability and allows for controlled release. Encapsulation of drugs into functional nanocarriers enhances their specificity, targeting ability, efficiency, and effectiveness. Functionality may come from cell targeting biomolecules that direct nanocarriers to a specific cell or tissue. Delivery is usually mediated by diffusion and erosion mechanisms, but in some cases, this is not sufficient to reach the expected therapeutic effects. This work reports on the development of a new photoresponsive polymeric nanocarrier (PNc)-based nanobioconjugate (NBc) for specific photo-delivery of cargo into target cells. We readily synthesized the PNcs by modification of chitosan with ultraviolet (UV)-photosensitive azobenzene molecules, with Nile red and dofetilide as cargo models to prove the encapsulation/release concept. The PNcs were further functionalized with the cardiac targeting transmembrane peptide and efficiently internalized into cardiomyocytes, as a cell line model. Intracellular cargo-release was dramatically accelerated upon a very short UV-light irradiation time. Delivering cargo in a time-space controlled fashion by means of NBcs is a promising strategy to increase the intracellular cargo concentration, to decrease dose and cargo side effects, thereby improving the effectiveness of a therapeutic regime. Functional nanocarriers for intracellular drug delivery are systems ideally composed of biodegradable and biocompatible materials such as natural polymers, lipids, amphiphilic polymers, among others, assembled with cell-targeting biomolecules (CTBs) 1,2. Nanocarriers can be designed for transporting a variety of cargo, either encapsulated into, adsorbed at, or dispersed with the nanocarriers 3. Encapsulation of therapeutic agents into nanocarriers protects them from degradation, improves their solubility and bioavailability, and enhances the efficiency and effectiveness of therapeutic regimens. However, nanocarrier systems have shown some limitations related to storage stability and administration route, because they are susceptible to aggregation and early degradation 4. Biodistribution may be also unspecific, generating inefficient therapies, side effects, genetic damage or mutations. To solve these issues, apart from carboxylic, amino, poly(ethylene glycol) and poly(phosphoester) moieties that can be placed at the outermost nanocarrier surface to confer a stealth effect, they can be functionalized with specific CTBs for site-specific controlled cargo release 5-7. Targeting ability and specificity of the resultant NBcs allows them to accumulate in the target cell or tissue at higher concentrations compared to nanoparticles without activity, thus reducing doses, frequency, toxicity and potential adverse effects that most drugs intrinsically have 8,9. Whereas the small size of NBcs, which are commonly less than 200 nm for biomedical applications 10,1...

Advances in Functionalized Photosensitive Polymeric Nanocarriers

“…The improved cellular uptake was explained by the peptide-coated nanocarriers' capacity to disrupt the cardiomyocyte's cell membrane. Therefore, intracellular cargo release was dramatically accelerated upon short UV-light irradiation (Figure 4) [99].…”

“…The resultant LRNs were functionalized with a FITC-CTB for the enhanced uptake by cardiomyocyte cells. The photoactive groups suffer a reversible isomerization from cis to trans by UV absorption and trans to cis by visible light, destabilizing the nanostructures, thus releasing the cargo into the cells [99]. Another interesting approach was a photoinduced scission of azo-modified polymer brushes covalently linked to a solid surface [116].…”

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

“…However, such mechanisms have evolved towards more refined ones based on physical, chemical, or biochemical external stimuli. In this context, triggered local changes in pH and temperature, in the number of reactive oxygen species (ROS), the reductive or oxidative states, and conformational changes in the polymer have been extensively used [ 14 , 15 , 32 ].…”

Smart Nanomaterials for Biomedical Applications—A Review

“…They used photoresponsive polymeric nanocarriers functionalized with a cardiac transmembrane peptide. The viability of the therapeutic regime was improved by the effect of UV light irradiation which increases the concentration of intracellular delivery and decreases the amount and cargo reactions [70]. In Figure 4 A group of authors anchored uniform zeolitic imidazolate framework (ZIF-8) crystals onto FeOOH nanorods through a simple recombination process to obtain FeOOH@ZIF-8 composites for in vitro direct metabolic analysis of biofluids in diagnostics of gynecological cancers.…”