Cancer is a dynamic disease characterized by its heterogeneous nature. This heterogeneity results in critical problems that interfere with the eradication of cancer tumors such as multidrug resistance, drug efflux capacity, narrow therapeutic window, and undesired side effects. Nanomedicine has introduced new platforms for drug delivery to enhance therapeutic efficiency of anticancer drugs. In addition to drug delivery, nanocarriers such as liposomes, carbon nanotubes, quantum dots, polymeric nanoparticles, dendrimers, and metallic nanoparticles can be designed for detection, diagnosis, and treatment. Recent studies support the idea that a combination of two or more nanoparticle‐mediated therapies can result in a synergistic therapeutic outcome to improve current cancer treatments. In this progress report, recent advances in nanoparticles‐based combination therapies are discussed. A brief overview of the complexity of cancer tumor's microenvironment is presented, followed by discussion of combinatorial therapies categorized based on chemotherapeutic agents, nucleic acid or therapeutic proteins, energy‐based therapies and imaging techniques for theranostic application. Different nanotechnological platforms are developed for combination therapy as tools with a great potential to tackle the most critical issues of current cancer treatments. A deeper understanding of these nanotechnologies and their possible long‐term effects in biological systems is needed for further clinical translation.
Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at sustained therapeutic levels. Here, we report synthesis of porous silicon nanoparticles conjugated with gold nanorods [composite nanoparticles (cNPs)] and encapsulate them within a hybrid polymersome using double-emulsion templates on a microfluidic chip to create a versatile nanovehicle. This nanovehicle has high loading capacities for both hydrophobic and hydrophilic drugs, and improves drug delivery efficiency by accumulating at the tumor after i.v. injection in mice. Importantly, a triple-drug combination suppresses breast tumors by 94% and 87% at total dosages of 5 and 2.5 mg/kg, respectively, through synergy. Moreover, the cNPs retain their photothermal properties, which can be used to significantly inhibit multidrug resistance upon near-infrared laser irradiation. Overall, this work shows that our nanovehicle has great potential as a drug codelivery nanoplatform for effective combination therapy that is adaptable to other cancer types and to molecular targets associated with disease progression.
more » « less- NSF-PAR ID:
- 10091549
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 116
- Issue:
- 16
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- p. 7744-7749
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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