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.

Background: Cancer is a complex heterogeneous disease to which singular modes of treatment mostly fail to produce a desired therapeutic efficacy. Targeting different cellular pathways using combinational therapies has been gaining popularity in cancer treatment, with the added benefit of reducing dosage and side effects. Methods: A gold nanoparticle-mediated drug delivery nanoplatform was developed for co-delivery of doxorubicin and polo-like kinase 1 (PLK1) siRNA. Gold nanoparticles were coated with polyethyleneimine to facilitate assembly of PLK1 on the surface. Doxorubicin was loaded on nanoparticles through a pH-sensitive linker with a thiol group at one terminal end for controlled release. Results: The therapeutic efficiency of this co-delivery system was evaluated in 2D and 3D cultured systems. The reduced IC₅₀ value clearly demonstrated the synergistic effect of combined drug and gene delivery over their individual delivery in a cancer treatment model. Conclusion: This study may provide an adaptable, facile platform to investigate drug-siRNA combinations for cancer inhibition.

Cancer is a heterogeneous and complex disease. Traditional cancer therapy is associated with low therapeutic index, acquired resistance, and various adverse effects. With the increasing understanding of cancer biology and technology advancements, more strategies have been exploited to optimize the therapeutic outcomes. The rapid development and application of nanomedicine have motivated this progress. Combinational regimen, for instance, has become an indispensable approach for effective cancer treatment, including the combination of chemotherapeutic agents, chemo-energy, chemo-gene, chemo-small molecules, and chemo-immunology. Additionally, smart nanoplatforms that respond to external stimuli (such as light, temperature, ultrasound, and magnetic field), and/or to internal stimuli (such as changes in pH, enzymes, hypoxia, and redox) have been extensively investigated to improve precision therapy. Smart nanoplatforms for combinational therapy have demonstrated the potential to be the next generation cancer treatment regimen. This review aims to highlight the recent advances in smart combinational therapy.