Cancer Nanomedicine: Shaping New-Generation Therapies

Nanotechnology has generated huge interest in the diagnosis and treatment of cancer. Interest in cancer nanomedicines has gained significant momentum in both the public eye as well as the scientific community, as more than 10 million people are diagnosed with cancer every year.

Conventional therapies are non-selective, non-specific, and non-discriminating small molecules that can be distributed all over the body and might result in many undesirable side effects and drug resistance.

Nanomedicine has the potential to improve anticancer therapy compared to traditional therapies by utilizing the ability to focus on targeting different cells within an organ. This organ-level distribution of nanoparticles substantially improves the quality of the immunological response.

To delve more into this, nanomedicine has shown remarkable efficiency in lymph-node-specific deliveries, as lymph nodes provide an appropriate environment for the survival and proliferation of immune cells. This initiates prominent adaptive immunity, which is required for maximizing the efficacy of immune drugs. 

Lymphatic System in Tumors

White blood cells and proteins are being ferried inside the human body through tiny lymphatic vessels that are compromised in infectious diseases and metastatic conditions. Following the efficient lymphatic drainage system, cancer cells enter the lymphatic vessels and then the lymph nodes. This is enabled by the capability of lymphatic vessels to provide a route for the tumor cells to reach regional lymph nodes.

Cancer-induced lymphangiogenesis (i.e., the process of generation of new lymphatic vessels) is a prominent indicator of vigorous metastasis to lymph nodes and can hence also be an evident target for anti-lymphangiogenic cancer treatment strategies.

The immune response is regulated by secondary lymphoid organs (spleen and lymph nodes) that are important for tumor development, as well as immunotherapy, wherein antigen-presenting cells and complimentary antibodies are delivered to the LNs via lymphatic fluid. Subsequently, this initiates adaptive immunity by activating antigen-specific T cells and transporting them to the target site.  

Nanomedicine as a Potential Therapy

Healthcare innovation involves the application of nanotechnology, primarily nanomedicines, in the oncology domain. The nanomedicine-based modification of oncology drugs can help to modulate the behavior of myeloid and lymphoid cells, thereby enhancing anticancer immunity and immunotherapy efficacy. Immunotoxic effects were majorly induced upon intravenous administration of these nanomaterials when these interact with blood constituents. The ability of lymph nodes to accumulate and retain many immune functional compounds from blood enhances their efficacy in subsequent therapy.

Targeted drug delivery can be increased by utilizing nano-delivery systems containing APCs targeting ligands, wherein the nanoparticles are surface-modified. These are then transported to lymphoid tissues, resulting in an increased concentration of the drug in the LNs. This specific interaction of surface-modified nanoparticles and lymphoid organs results in improved anti-tumor effects and reduced off-target side effects.

Nanomedicine has been keenly applied in oncological studies and a significant impact has been studied. Herein, the majority section of the nanomedicine has been included in the clinical studies. Below is presented a generic version of the number of clinical trials specific to conditions –

Fig 1. Generic Indication-Based Segregation of Clinical Trials Reported till Date

Simplifying and associating the physiological functioning of lymphoid organs and nano delivery systems can result in much more efficient production of required anti-tumor nanoparticles.

These specific nanoparticles should possess appropriate properties for successful accumulation in the lymph nodes. This includes surface properties involving size, surface charge, and ability to deform to accommodate inside lymph conduits. For example, α-Melittin-NPs are spherical nanoparticles with a size of below 30 nm and are easily diverted to lymphatic vessels and LNs.

Lymph node-targeting nanoparticles rely upon the type of material being utilized for site-specific targeting. To enhance the site-specific delivery, targeted nanoparticles named ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles have been advanced in mice. These depend upon lymphatic drainage and further reach the lymph nodes and blood. They enter the spleen rather than the liver, where they interact with monocytes, macrophages, and myeloid dendritic cells.

Further, cancer nanomedicines, if co-loaded with drugs, can also be co-loaded with imaging agents to visualize and quantify target site accumulation directly. In this case, one of the applicable major drainage filters is the size-dependent lymphatic drainage and uptake pathways, wherein particles less than 100nm can freely drain to the lymph nodes.

A few of the FDA-approved anti-cancer drugs formulated as nanomedicine are presented below-

Table 1. FDA/EU Approved Anti-cancer Nanomedicine Drugs

Market Trends & Major Competitors

Apart from the major vaccine market players, there are a few companies exclusively working in cancer nanomedicines. However, there are a few nanomedicine research centers and producers that provide a promising avenue for further growth in this field. In accordance with this, many researchers at the Frederick National Laboratory for Cancer Research (FNL) are currently developing a nanotechnology platform that would target the lymphatic system. This significant approach could provide more effective treatment and therapies against infectious diseases and cancer.

Currently, there are not many market players working specifically for lymphatic drainage nanomedicine for cancer. However, research is on swing in a number of universities, including the University of Kansas among others.

The major players globally working in the field of nanomedicine are presented below –

Fig 2: Major Nanomedicine Contributors

Conclusion

Focusing upon new-age cancer therapeutics wherein the currently existing therapies have particular toxic side effects, lymphoid organs targeting nanoparticles containing anti-tumor therapeutics are being valued. Tumor-draining lymph nodes are prominent for presenting tumor antigens to the immune system and are seen as potential targets of importance for cancer vaccines.

By targeting lymph nodes associated with tumors, it is possible to modulate the immunological response to promote anti-tumor immunity and prevent immune tolerance, ultimately enhancing the effectiveness of cancer vaccines. Also, it has been experimentally noticed that interstitial vaccination is the primary method of vaccine administration to target LNs.

In accordance with all the above aspects, the key solution lies in the combination of the right drug selection and the right regimen, which would generate appropriate results for the right disease indication and the right patient population. Therefore, achieving the clinical translation of tumor nano vaccines still requires considerable work.