Chemotherapeutic Drug Delivery Vehicle Based on Nanobodies

Nb-Based Drug Vehicles (NDv)

In recent years, there have been groundbreaking advancements in targeted therapy for tumors. One of these is the chemotherapeutic drug delivery vehicle based on Nbs. Slightly different from nanobody-drug conjugates (NDCs), NDv refers to a strategy that modifies nanobodies onto nano-drug carriers (such as liposomes, micelles, albumin, ferritin-like nanoparticles, polymer-based micelles, etc.), utilizing nanobodies to target specific antigens for targeted therapy on tumor cells. NDv exhibits high specificity, drug protection, controlled drug release, and tissue penetration, enabling more precise, effective, and safe drug delivery and treatment.

Advantages of NDv

Compared to delivery vehicles using mAbs, the small size of Nbs increases the stability and controlled orientation of the vector. Moreover, NDv boasts a superior capacity for carrying drugs when compared to NDC. What's more, the spacious interior of NDv allows for the incorporation of variously sized drug molecules, be they hydrophilic or hydrophobic. The strategic adaptation or modification of NDv with specific molecules allows for the fine-tuning of ADME processes, thereby significantly altering pharmacokinetics. This, in turn, effectively mitigates the side effects of adherent drugs, such as nonspecific interactions with healthy cells, low stability, formation of coronal proteins, susceptibility to immune attacks, drug leakage, and reproducibility issues. Consequently, it markedly amplifies drug-targeting precision and therapeutic efficacy.

The versatility of NDv extends beyond the realm of conventional chemotherapeutic drug delivery. It seamlessly integrates with other innovative therapeutic strategies, including immunotherapy and gene therapy, forming a comprehensive, multi-therapeutic treatment approach. This integrated strategy not only tackles drug resistance in cancer cells but also minimizes the harmful impact of chemotherapeutic drugs on healthy tissues, ultimately bolstering the anti-tumor efficacy of drugs. This amalgamation promises a more precise, effective, and sustainable anti-cancer treatment modality, catering to the specific needs of individual patients.

NDv in Tumor Treatment

The ongoing exploration into NDv applications in tumor treatment has unveiled cutting-edge strategies for NDv construction, encompassing an array of pioneering methods such as polymer micelles (PMs), dendrimer nanoparticles, nanoscale DNA carriers (TET), upconversion nanoparticles (UCNPs), albumin nanoparticles, and liposomes.

Liposomes, characterized as minute spherical vesicles boasting an aqueous core encased by a lipid bilayer, are primarily constituted of naturally occurring amphipathic phospholipids and cholesterol, minimizing the likelihood of immune responses. Remarkably versatile, liposomes can be finely tailored in size and possess commendable hydrophilic and hydrophobic properties, rendering them an ideal conduit for delivering chemotherapeutic drugs. A notable advancement includes the conjugation of nanobodies to liposomes, giving rise to nanobody-liposome complexes geared for targeted drug delivery.

In parallel, polymeric micelles (PMs), minute complexes of amphiphilic molecules self-assembling in aqueous solutions, have garnered considerable attention. Renowned for their biocompatibility, heightened stability, and capacity to solubilize less soluble drugs, PMs exhibit a proclivity for accumulating in areas of pathologically impaired blood vessels, further solidifying their significance in the field.

Dendrimer nanoparticles, constructed from polymer compositions with a radial branching structure, boast an impressive set of advantages, including controllable synthesis, favorable solubility, elevated biocompatibility, multi-valent external surfaces, and prolonged stability. Hence, in the realm of targeted cancer therapy, they emerge as a favorable candidate for effective drug loading.

Further expanding the horizons of NDv applications, the manipulation of DNA molecules to form intricately designed nano-sized folding structures has emerged as a promising avenue. These nanoscale DNA carriers (TET) hold the potential for loading chemotherapeutic drugs or agents targeting specific cells, with programmable capabilities to instigate cellular responses within the biological microenvironment.

Combining drugs with a nanobody-based carrier (i.e., NDv) represents an emerging drug delivery system that overcomes the limitations of chemotherapy, achieving precise delivery to cancer cells and significantly reducing side effects. The nanoscale size, high solubility, stability, low immunogenicity, deep tumor penetration capability, exceptional specificity, and high affinity for cancer biomarkers of nanobodies (Nbs) make them ideal targeting molecules. A thorough understanding of the interaction between nanobodies and cancer biomarkers/antigens is crucial for fully harnessing the potential of NDv in chemotherapy.

References

1. Panikar S. S.; et al.Nanobodies as efficient drug-carriers: progress and trends in chemotherapy. Journal of Controlled Release. 2021, 334: 389-412.
2. Hu Y.; et al. Nanobody-based delivery systems for diagnosis and targeted tumor therapy. Frontiers in Immunology. 2017, 8: 1442.