“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Abstract

a b s t r a c t a r t i c l e i n f oThe dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

“…Hence, it is a feasible approach for cancer chemotherapy that an excellent Co-NDDS with a sequential and precision release characteristic can transport anticancer drugs to their pharmacological targets. 16,17 As mentioned, drugs in Co-NDDS should have different pharmacological target points. So, we selected two smallmolecule anticancer chemotherapeutic agents, vincristine (VCR) and DOX, as the model drugs for this study.…”

Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia

“…33 ABT-737 can induce cell apoptosis through selective inhibition of Bcl-xL and BCL-2, while also having no effect on MCL1. IRAK1/4 inhibitor can dramatically reduce MCL1 level in T-ALL cells.…”

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

“…16,17 Nevertheless, the translation of nanocarrier-based combination therapy into the clinic remains extremely challenging, and none of the products have been approved until now. 5,9 Alongside the complexity of physicochemical variability, safety concerns and regulatory and manufacturing issues, 18 major obstacles also lie in the difficulty in achieving efficient co-delivery of multiple chemotherapeutics, accurate drug-loading ratio and controlled synchronous release, especially for immiscible hydrophilic/hydrophobic drugs. [19][20][21] Consequently, development of nanocarriers that can provide efficient co-delivery of immiscible hydrophilic/ hydrophobic drugs with mature technology for industrial production is crucial.…”

“…1 Combination chemotherapy is widely employed in clinics, 2,3 with the objective of improving therapeutic effect and decreasing drug resistance, by targeting a single oncogenic pathway through different modes of action or across multiple interrelated pathways. [4][5][6] Taking into account that the traditional administration in clinics is just a simple cocktail, the uncoordinated pharmacokinetics and uncontrolled release properties of different drugs restrict their applications, leading to the uncertainty of treatment. 7,8 Nanomedicine approach of synergistic drug combinations can normalize pharmacokinetics and pharmacodynamics of the active agents, control the synchronous release in target site and provide superior therapeutic effects.…”

“…7,8 Nanomedicine approach of synergistic drug combinations can normalize pharmacokinetics and pharmacodynamics of the active agents, control the synchronous release in target site and provide superior therapeutic effects. 5,9 Several different types of nanocarriers have been developed to co-deliver multiple drugs such as liposomes, micelles and mesoporous silica. 10,11 Liposomes could encapsulate both hydrophilic and hydrophobic drugs due to the special core/shell structure.…”