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Advances in Smart and Innovative Nanoparticles for Precision Tumor Therapy:...
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Advances in Smart and Innovative Nanoparticles for Precision Tumor Therapy: Design, Delivery, Immune Modulation, and Clinical Translation

A Special Issue of Cells (ISSN 2073-4409) belonging to the section "Cell Methods".

Deadline for manuscript submissions: closed (31 July 2026) | Viewed by 4841

Editors

Dr. Hari Krishnareddy Rachamala

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, FL 32224, USA
Interests: nanomedicine; cancer immunotherapy, radiation therapy and AI-driven drug discovery, with particular emphasis on lipid/polymeric nanoparticle-based drug and mRNA delivery systems and personalized cancer vaccines; developing targeted therapeutics and advanced delivery platforms for solid tumors
Special Issues, Collections and Topics in MDPI journals
Dr. Naga Malleswara Rao Nakka

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Mayo Clinic, Jacksonville, FL 32224, USA
Interests: polymer chemistry; nanomedicine; biodegradable polymers; targeted drug delivery; gene delivery; vaccine delivery; nanotechnology; cancer therapy; biomaterials

Special Issue Information

Dear Colleagues,

Recent advances in nanotechnology have revolutionized cancer therapy by enabling the development of smart and innovative nanoparticles designed for precision tumor targeting. These nanoplatforms integrate advanced materials, stimuli-responsive systems, and biomimetic strategies to enhance drug delivery, improve tumor penetration, and minimize off-target toxicity. Beyond conventional cytotoxic payloads, next-generation nanoparticles incorporate immunomodulatory agents to reprogram the tumor microenvironment and synergize with immunotherapies. Innovations in design, including ligand-mediated targeting, controlled release mechanisms, and real-time theranostic capabilities, are bridging the gap between preclinical success and clinical translation. Collectively, these technologies hold the potential to transform oncology by offering more effective, personalized, and durable therapeutic outcomes for patients with challenging malignancies.

Dr. Hari Krishnareddy Rachamala
Dr. Naga Malleswara Rao Nakka
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • smart nanoparticles
  • tumor-targeted drug delivery
  • immune modulation
  • stimuli-responsive nanocarriers
  • clinical translation in oncology

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Published Papers (2 papers)

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19 pages, 4150 KB  
Article
Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity in Osteosarcoma
by Namrata Anand, Joseph Robert McCorkle, David S. Schweer, Lan Li, Kristen S. Hill, Melissa A. Fath, Derek B. Allison, Christopher L. Richards and Jill M. Kolesar
Cells 2025, 14(20), 1616; https://doi.org/10.3390/cells14201616 - 17 Oct 2025
Cited by 9 | Viewed by 3640
Abstract
Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to [...] Read more.
Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to a poor antigenic tumor microenvironment. Here, we address these challenges by using manufactured M1 macrophage-derived vesicles (MVs) loaded with cisplatin. Human blood and mouse RAW 264.7 M1 macrophages were used to prepare empty (E-MVs) and cisplatin-loaded MVs (C-MVs). Human OS cell lines were used in vitro and in a tibia xenograft mouse model to evaluate the anti-cancer and immune-stimulating abilities of MVs. C-MVs had lower IC50s but equivalent DNA damage in OS cell lines when compared with free cisplatin. E-MVs and C-MVs were observed to accumulate in the tumor in OS tumor-bearing mice. C-MVs significantly reduced tumor burden and prolonged survival in a mouse model of OS. Animals dosed with free cisplatin experienced weight loss and renal and hepatic toxicity, while equivalent doses of C-MVs did not cause these effects. In addition, both E-MVs and C-MVs showed immunomodulation of the tumor microenvironment with a significant increase in the M1/M2 macrophages ratio (7-fold and 22-fold, respectively) and increased levels of TNF-α in serum (1.8-fold and 2.1-fold, respectively) compared to control mice. Collectively, these experiments support further development of C-MVs for the treatment of OS. Full article
(This article belongs to the Special Issue Advances in Smart and Innovative Nanoparticles for Precision Tumor Therapy: Design, Delivery, Immune Modulation, and Clinical Translation)
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12 pages, 865 KB  
Perspective
Smart Nanoparticles Are Not Smart Enough (Yet): A Cell-Aware View of Cancer Nanomedicine
by Serena Marchiò
Cells 2026, 15(6), 491; https://doi.org/10.3390/cells15060491 - 10 Mar 2026
Viewed by 663
Abstract
“Smart” nanoparticles are often presented as the vanguard of precision cancer therapy, defined by engineered abilities to sense predefined stimuli, enhance targeting, and control therapeutic release. Yet this notion of smartness remains largely material-centric and only partially reflects how nanomedicines behave in vivo. [...] Read more.
“Smart” nanoparticles are often presented as the vanguard of precision cancer therapy, defined by engineered abilities to sense predefined stimuli, enhance targeting, and control therapeutic release. Yet this notion of smartness remains largely material-centric and only partially reflects how nanomedicines behave in vivo. Cells exposed to nanoparticles are not passive recipients of engineered functions; they actively interpret these perturbations through integrated stress-response, metabolic, transcriptional, and innate immune programs. These cell-state trajectories can determine efficacy, tolerance, resistance, or toxicity, and can do so independently of uptake, biodistribution, or triggerable release efficiency. Accordingly, evaluation strategies that prioritize delivery metrics and limited a priori molecular markers may misestimate functional performance and durability. This Perspective proposes a cell-aware reframing in which smartness is defined by biological controllability: the capacity of a nanoparticle system to elicit predictable, mechanistically interpretable, and therapeutically favorable cell-state trajectories across relevant malignant and non-malignant compartments. A practical path forward is to integrate time-resolved functional profiling into benchmarking using compact response signatures that report stress buffering, immune activation or suppression, and the emergence of tolerant states. A practical path forward is to integrate time-resolved functional profiling into benchmarking using compact response signatures that report stress buffering, immune activation or suppression, and the emergence of tolerant states. Here, biological controllability refers to the ability of a nanoparticle system to reproducibly steer integrated cellular stress, metabolic, and immune programs toward predefined therapeutic endpoints while minimizing adaptive escape across heterogeneous compartments. Full article
(This article belongs to the Special Issue Advances in Smart and Innovative Nanoparticles for Precision Tumor Therapy: Design, Delivery, Immune Modulation, and Clinical Translation)
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