Tailorable drug delivery systems for combination therapy
Advances in nanotechnology have led to the development of multifunctional nanoparticles that allow the delivery of multiple drugs, nucleic acids, targeting moieties, and imaging agents to diseased tissue. Due to heterogeneity of tumor tissues and drug resistance mechanisms, many cancer patients may benefit from treatments combining multiple therapeutics [9]. Combination therapies which include multiple drugs and gene therapy have been proven to increase drug sensitivity and therapeutic efficacy, particularly in cancer treatment [10,11]. Liposomal nanoparticles are ideal for combination therapy due to the ability to tailor their properties including size, surface charge and hydrophobicity. Alternating hydrophilic and lipophilic regions within the lipid bilayers of liposomes allow loading of both hydrophilic and hydrophobic drugs. Nucleic acids can also be encapsulated in various types of charged liposomes for gene therapy. For instance, stable nucleic acid lipid particles (SNALPs) are liposomes that have neutral outer surfaces and allow nucleic acid loading through electrostatic interaction with cationic lipids in the interior [12]. Lipoplexes offer similar capabilities in which nucleic acids may be embedded between cationic lipid bilayers of the multilamellar liposomes [12]. Additionally, multifunctionality can be created by conjugating targeting moieties and incorporating imaging agents to enable cell/tissue specific uptake and image-guided therapy, respectively [13,14]. Therefore, our lab is developing multifunctional SNALPs and lipoplexes that enable tailorable combination therapy for the treatment of various cancers.
References​
[9] Komarova NL, Boland CR. Cancer: Calculated treatment. Nature. 2013; 499(7458):291-2.
[10] Lopez JS, Banerji U. Combine and conquer: challenges for targeted therapy combinations in early phase trials. Nature reviews Clinical oncology. 2016.
[11] Tsouris V, Joo MK, Kim SH, Kwon IC, Won YY. Nano carriers that enable co-delivery of chemotherapy and RNAi agents for treatment of drug-resistant cancers. Biotechnology advances. 2014; 32(5):1037-50.
[12] Xia Y, Tian J, Chen X. Effect of surface properties on liposomal siRNA delivery. Biomaterials. 2016; 79:56-68.
[13] Kono K, Takashima M, Yuba E, Harada A, Hiramatsu Y, Kitagawa H, et al. Multifunctional liposomes having target specificity, temperature-triggered release, and near-infrared fluorescence imaging for tumor-specific chemotherapy. Journal of Controlled Release. 2015; 216:69-77.
[14] Xiang B, Dong D-W, Shi N-Q, Gao W, Yang Z-Z, Cui Y, et al. PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer. Biomaterials. 2013; 34(28):6976-91.