Marina Pinheiro1,2*
Qingxin Mu3*- 1Department of Chemistry, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
- 2Public Health Unit, Local Health Unit Barcelos/Esposende, Barcelos, Portugal
- 3Department of Pharmaceutics, University of Washington, Seattle, WA, United States
Editorial on the Research Topic
Editor’s challenge: Dr. Qingxin Mu - how can nanomedicine approaches advance multi-targeting strategy in combination cancer therapy?
Cancer remains a prominent global cause of death despite numerous advancements in prevention, diagnosis, and treatment approaches (1, 2). Combination therapy, which address multiple therapeutic targets, can exert pharmacological synergy and reduce dose-limiting toxicity of single agents, and have shown enhanced treatment outcomes in patients (3). However, owing to several challenges such as asynchronous circulation of drugs and lack of cancer cell specificity, the therapeutic synergy and overall outcomes of combination regimens may be suboptimal (4). Nanomedicine, as an innovative strategy in oncology research, has progressively matured over the past few decades. Currently, various nanomedicine approaches have been successfully utilized in both clinical and preclinical applications, ranging from imaging to drug delivery including combination therapeutic delivery, and have improved health outcomes (5–7). For example, Vyxeos® is a US FDA-approved nano-liposomal co-formulation of daunorubicin and cytarabine for combination treatment of secondary acute myeloid leukemia (8). Nonetheless, broad applications of nanomedicine approaches for improved combination therapy are still lacking. In this Research Topic entitled “Editor’s Challenge: Dr. Qingxin Mu – How can Nanomedicine Approaches Advance Multi-Targeting Strategy in Combination Cancer Therapy?”, we have gathered a few outstanding contributions highlighting nanomedicine as a new and promising strategy to improve combination therapy of cancer. The Research Topic contains 5 articles, namely 3 research articles, 1 review and 1 mini-review. The complete description of each study and the main results are presented in the full manuscripts and readers are pleasantly invited to explore the contents in full detail.
In the manuscript written by Donovan et al., the authors provided scientific evidence and demonstrated that when combining specific FOXM1 inhibitor RCM1 loaded in poly-beta-amino esters and folic acid-containing nanoparticle delivery with low doses of vincristine for treatment, increased rhabdomyosarcoma (RMS) cell apoptosis and decreased proliferation were observed in vitro compared to single drugs alone. The combination therapy was safe as demonstrated by liver metabolic panels using peripheral blood serum. The authors also used RNA-seq of dissected RMS tumors and identified Chac1 as a uniquely downregulated gene after the combination treatment. Lastly, through an RNA depletion assay, the authors verified that the knockdown of Chac1 in RMS cells in vitro recapitulated the effects of the combination therapy.
Salman-Javan et al. authored a manuscript showing that the use of PEGylated niosomal nanoparticles synthesized via the thin-film hydration method and co-loaded with metformin and silibinin improved the therapeutic efficiency in lung cancer cells through synergistic effects compared to the individual therapies. Mechanistically, with qRT-PCR assay, they found that the metformin-silibinin combination notably decreased in the expression of hTERT and BCL-2 genes, accompanied by an increase in BAX expression in the treated A549 lung cancer cells. More importantly, the suppression of hTERT and BCL-2 expression and the elevation of BAX gene expression were significantly heightened when A549 cells were treated with the drug combination encapsulated in PEGylated niosomal nanoparticles.
In the manuscript written by Kauser et al., the authors developed an Artemisia absinthium extract-loaded nanoformulations using N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid-based polymeric nanoparticles. The authors employed nano LC-MS/MS to identify differences in secretory protein expression associated with the treatment of breast cancer cell lines (MCF-7 and MDA-MB-231) and performed several bioinformatics analyses. Their results demonstrated that the formulations were able to invade the breast cancer tumor microenvironment, transform the communication network between the cancer cells, affect potential drivers of microtubular integrity, nucleosome assembly, and cell cycle; and eventually cause cell death.
The manuscript of Liao et al. highlighted the autophagy-mediated nanomaterials’ therapeutic efficacy and potential applications. The autophagy signaling pathway for tumor therapy was reviewed, including oxidative stress, mammalian target of rapamycin (mTOR) signaling and autophagy-associated genes pathway. This manuscript provides a comprehensive review of the different autophagy-mediated nanomaterials that have been developed and applied in tumor therapy. Several combination approaches for enhanced autophagy-inducing effects were also discussed.
Last but not least, the mini-review written by Linde et al. provides an overview of the recent investigations in nanoparticles strategies for improving PD-1/PD-L1 blockade-based combination therapy for triple-negative breast cancer (TNBC). In this review, the authors discussed in detail how nanotechnology can be used in combination with existing treatments. The authors concluded that nanomedicine approach represents a promising avenue for enhancing PD-1/PD-L1 blockade-based combination therapy for TNBC and encourages further development studies.
In summary, the original findings as well as critical reviews in this Research Topic have demonstrated nanomedicine as a promising strategy for developing more effective cancer combination therapies. Further extensive studies such as in-depth preclinical and clinical investigations and formulation developments, are encouraged.
Author contributions
MP: Writing – review & editing, Writing – original draft. QM: Writing – review & editing, Writing – original draft.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. QM was supported by NIH grant R21CA273739 for this work.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. (2024) 74:12–49. doi: 10.3322/caac.21820
2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. (2024) 74:229–63. doi: 10.3322/caac.21834
3. Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget. (2017) 8:38022–43. doi: 10.18632/oncotarget.16723
4. Fudio S, Sellers A, Pérez Ramos L, Gil-Alberdi B, Zeaiter A, Urroz M, et al. Anti-cancer drug combinations approved by US FDA from 2011 to 2021: main design features of clinical trials and role of pharmacokinetics. Cancer Chemotherapy Pharmacol. (2022) 90:285–99. doi: 10.1007/s00280–022-04467–7
5. Giri PM, Banerjee A, Layek B. A recent review on cancer nanomedicine. Cancers. (2023) 15:2256. doi: 10.3390/cancers15082256
6. Nirmala MJ, Kizhuveetil U, Johnson A GB, Nagarajan R, Muthuvijayan V. Cancer nanomedicine: a review of nano-therapeutics and challenges ahead. RSC Adv. (2023) 13:8606–29. doi: 10.1039/D2RA07863E
7. Mu Q, Yu J, McConnachie LA, Kraft JC, Gao Y, Gulati GK, et al. Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook. J Drug Targeting. (2018) 26:435–47. doi: 10.1080/1061186X.2017.1419363
Keywords: nanomedicine, nanoparticles, drug delivery, combination therapy, multi-targeted
Citation: Pinheiro M and Mu Q (2024) Editorial: Editor's challenge: Dr. Qingxin Mu - how can nanomedicine approaches advance multi-targeting strategy in combination cancer therapy? Front. Oncol. 14:1437497. doi: 10.3389/fonc.2024.1437497
Received: 23 May 2024; Accepted: 04 June 2024;
Published: 11 June 2024.
Edited and Reviewed by:
Massimo Broggini, Mario Negri Institute for Pharmacological Research (IRCCS), ItalyCopyright © 2024 Pinheiro and Mu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Marina Pinheiro, mpinheiro@ff.up.pt; Qingxin Mu, qmu@uw.edu