Multifunctional nanoparticles are a promising system that can offer an opportunity to change the pharmacokinetic outline of drugs, reduce toxicity, and enhance therapeutic markers. Additionally, cancer nanotechnology could open up opportunities for screening cancer diagnosis and treatment approaches through multifunctional nanoparticles in four main areas: imaging tumors, detecting cancer disease biomarkers, targeting tumor cells with treatment modalities on the surface and in the core, and monitoring treatment to apply effective combinatorial therapeutic regimens against cancer (1). In this blog, I will explain more details about the usage of multifunctional nanoparticles in lung cancer and introduce different types of therapeutic nanoparticles.
Liposomes loaded with co-delivery of three different siRNA and one miRNA agents, which use an active or passive loading scheme, will enhance the formulation of combinatorial nanoparticles and the removal of unloaded drugs. For lung cancer, targeted liposomes can be used to co-deliver DOX and DNA encoding to regulate the mutant of survivin in human cancers. Survivin is a member of the inhibitor of apoptosis protein family and is expressed in a large variety of malignancies (2). The liposomal drug delivery technique combined truncated basic fibroblast growth factor (TBFGF) peptides that identify BFGF receptors overexpressed in lung cancer with DOX and pDNA encoding for the negative mutant of survivin to counter survivin-mediated apoptosis resistance (3). Co-delivering chemotherapeutic agents produced an improved therapeutic response against Lewis lung carcinoma tumors over liposomes with either agent alone. However, liposomes still face several limitations, one of which is poor stability. To enhance the transfection efficiency of plasmid co-delivery of DOX and DNA encoding, I would coat a liposome with hydrophilic polymers to prevent the liposome from being adsorbed to plasma proteins and from being phagocytosed by macrophages (4).
Another approach I have read about is a lung cancer targeted theranostic agent based on immunoliposomes for the inhibition of tumor growth and prevention of angiogenesis. Immunoliposomes are carriers used for drug delivery, and they have the ability to encapsulate both hydrophilic and hydrophobic therapeutic agents. In lung cancer, an anti-c-Met single chain variable fragment (scFv) antibody was first identified by (Ms20, Kd value; 9.14 nM) (4). Cysteine residues were then merged for site-directed combination with maleimide-modified PEG-terminated liposomal DOX. The final formulation resulted in Ms20-conjugated liposomal DOX, which enhances the chemotherapeutic drug delivery by inhibiting c-Met-transient or c-Met-constitutive activation of cancer cells (4). However, to improve the delivery and biodistribution of encapsulated agents, we need to consider liposomes, antibodies, and the chemotherapeutic agent. Liposomes with targeting antibodies can be achieved by crosslinking targeting antibodies to lipids or the terminal ends of PEG chains extending from the outer liposomal membrane. Additionally, the use of PEG can enhance circulation time but also reduce the proximity of adjacent antibody molecules on the surface of the liposome (5).
References
- Parvanian, Sepideh, Seyed Mojtaba Mostafavi, and Meysam Aghashiri. Multifunctional nanoparticle developments in cancer diagnosis and treatment.” Sensing and bio-sensing research 13 (2017): 81-87.
- Jaiswal, Praveen Kumar, Apul Goel, and R.D. Mittal. “Survivin: A Molecular Biomarker in Cancer.” The Indian Journal of Medical Research 141.4 (2015): 389–397.
- Glasgow, Micah D. K., and Mahavir B. Chougule. “Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging.” Journal of biomedical nanotechnology 11.11 (2015): 1859–1898.
- Wang, Wenxi, et al. “Cationic polymethacrylate-modified liposomes significantly enhanced doxorubicin delivery and antitumor activity.” Scientific reports 7 (2017): 43036.
- Brown, Brandon S et al. “Etoposide-Loaded Immunoliposomes as Active Targeting Agents for GD2-Positive Malignancies.” Cancer Biology & Therapy15.7 (2014): 851–861.
