Passing of Nanocarriers across the Histohematic Barriers: Current Approaches for Tumor Theranostics

Abstract

Over the past several decades, nanocarriers have demonstrated diagnostic and therapeutic (i.e., theranostic) potencies in translational oncology, and some agents have been further translated into clinical trials. However, the practical application of nanoparticle-based medicine in living organisms is limited by physiological barriers (blood–tissue barriers), which significantly hampers the transport of nanoparticles from the blood into the tumor tissue. This review focuses on several approaches that facilitate the translocation of nanoparticles across blood–tissue barriers (BTBs) to efficiently accumulate in the tumor. To overcome the challenge of BTBs, several methods have been proposed, including the functionalization of particle surfaces with cell-penetrating peptides (e.g., TAT, SynB1, penetratin, R8, RGD, angiopep-2), which increases the passing of particles across tissue barriers. Another promising strategy could be based either on the application of various chemical agents (e.g., efflux pump inhibitors, disruptors of tight junctions, etc.) or physical methods (e.g., magnetic field, electroporation, photoacoustic cavitation, etc.), which have been shown to further increase the permeability of barriers.

Targeted pH-Activated Peptide-Based Nanomaterials for Combined Photodynamic Therapy with Immunotherapy

“…RGD is a peptide ligand targeting αvβ3 integrins which are overexpressed by tumor vessels and by a wide variety of human cancer cells. , It is therefore often used for tumor-targeting treatments. RGD was included in our recently developed peptide-porphyrin conjugate (PWG), which was shown to form pH-responsive nanoparticles capable of PDT.…”

Recent Advances in Surface Functionalization of Magnetic Nanoparticles

“…This is a significant improvement over traditional methods where off-target effects can be a concern. The new functionalization techniques often lead to enhanced stability and longevity of the functionalized nanoparticles, surpassing traditional coatings that may be less robust while also affording the incorporation of multiple functionalities onto a single nanoparticle, allowing for synergistic effects [8,22,23]. Theranostics refers to combined therapy and diagnostics and represents a class of technologies that combine therapeutic and diagnostic capabilities in a single system.…”

“…Additional strides have been made in order to overcome biologic barriers such as the blood-brain barrier (BBB), and these consist of various functionalization of penetrating NPs with CPP (cell-penetrating peptides) such as hydrophilic (cationic; TAT, penetratin, R8), amphipathic (SynB, RGD, etc.) or hydrophobic (nonpolar, C105Y, PFV, Pep-7) [22]. An ongoing trend is to utilize MNPs in cell membrane-based biomimetic nanosystems for personalized disease theranostics including oncology, bacterial infections, brain diseases, and inflammatory diseases [23].…”

“…By combining targeted drug delivery with real-time imaging, researchers can develop personalized and optimized treatment strategies for cancer patients, minimizing side effects and maximizing therapeutic outcomes. This approach holds significant promise for the future of precision medicine in oncology [22,23].…”

“…The strategic surface functionalization of magnetic nanoparticles (MNPs) has revolutionized drug delivery, enabling precise and efficient therapeutic interventions. This section delves into the multifaceted enhancements brought about by surface engineering, including controlled drug release, targeted delivery, and overcoming biological and histohematic barriers [22]. Responsive and targeted drug delivery based on MNPs (magnetite Fe 3 O 4 mainly) coated with polymers and biopolymers [28], biomolecules or macromolecules (5-fluorouracil (5-FU), oxaliplatin, and irinotecan), can be successfully used for the treatment of various types of cancer, such as in colorectal cancer therapy [29].…”