Fast diagnosis and more efficient therapies for cancer surely represent one of the huge tasks for the worldwide researchers’ and clinicians’ community. In the last two decades, our understanding of the biology and molecular pathology of cancer mechanisms, coupled with the continuous development of the material science and technological compounds, have successfully improved nanomedicine applications in oncology. This review argues on nanomedicine application of engineered extracellular vesicles (EVs) in oncology. All the most innovative processes of EVs engineering are discussed together with the related degree of applicability for each one of them in cancer nanomedicines.

Zinc oxide nanoparticles (ZnO NPs) are currently among the most promising nanomaterials for theranostics. However, they suffer from some drawbacks that could prevent their application in nanomedicine as theranostic agents. The doping of ZnO NPs can be effectively exploited to enhance the already-existing ZnO properties and introduce completely new functionalities in the doped material. Herein, we propose a novel synthetic approach for iron-doped ZnO (Fe:ZnO) NPs as a multifunctional theranostic nanoplatform aimed at cancer cell treatment. Pure ZnO and Fe:ZnO NPs, with two different levels of iron doping, were synthesized by a rapid wet-chemical method and analyzed in terms of morphology, crystal structure and chemical composition. Interestingly, Fe:ZnO NPs featured bioimaging potentialities thanks to superior optical properties and novel magnetic responsiveness. Moreover, iron doping provides a way to enhance the electromechanical behavior of the NPs, which are then expected to show enhanced therapeutic functionalities. Finally, the intrinsic therapeutic potentialities of the NPs were tested in terms of cytotoxicity and cellular uptake with both healthy B lymphocytes and cancerous Burkitt’s lymphoma cells. Furthermore, their biocompatibility was tested with a pancreatic ductal adenocarcinoma cell line (BxPC-3), where the novel properties of the proposed iron-doped ZnO NPs can be potentially exploited for theranostics.

Conventional therapies to treat cancer often exhibit low specificity, reducing the efficiency of the treatment and promoting strong side effects. To overcome these drawbacks, new ways to fight cancer cells have been developed so far focusing on nanosystems. Different action mechanisms to fight cancer cells have been explored using nanomaterials, being their remote activation one of the most promising. Photo- and sonodynamic therapies are relatively new approaches that emerged following this idea. These therapies are based on the ability of specific agents to generate highly cytotoxic reactive oxygen species (ROS) by external stimulation with light or ultrasounds (US), respectively. Crystalline (TiO₂) and amorphous titania (a-TiO₂) nanoparticles (NPs) present a set of very interesting characteristics, such as their photo-reactivity, photo stability, and effective bactericidal properties. Their production is inexpensive and easily scalable; they are reusable and demonstrated already to be nontoxic. Therefore, these NPs have been increasingly studied as promising photo- or sonosensitizers to be applied in photodynamic/sonodynamic therapies in the future. However, they suffer from poor colloidal stability in aqueous and biological relevant media. Therefore, various organic and polymer-based coatings have been proposed. In this work, the role of a-TiO₂ based NPs synthesized through a novel, room-temperature, base-catalyzed, sol-gel protocol in the generation of ROS and as an enhancer of acoustic inertial cavitation was evaluated under ultrasound irradiation. A novel biomimetic coating based on double lipidic bilayer, self-assembled on the a-TiO₂-propylamine NPs, is proposed to better stabilize them in water media. The obtained results show that the biomimetic a-TiO₂-propylamine NPs are promising candidates to be US responding agents, since an improvement of the cavitation effect occurs in presence of the developed NPs. Further studies will show their efficacy against cancer cells.

Nanomedicine is an emerging treatment approach for many cancers, characterized by having high sensitivity and selectivity for tumor cells and minimal toxic effects induced by the conventional chemotherapeutics. In these context, smart nanoparticles (NPs) are getting increasingly relevant in the development of new therapies. NPs with specific chemical composition and/or structure and being stimuli-responsive to magnetic, light or ultrasound waves are new promising tools. In the present work, amorphous-titania propyl-amine functionalized (a-TiO₂-NH₂) NPs, coated with bovine serum albumin (BSA), are stimulated with high energy shock waves to induce cytotoxic effects in cancer cells. First, a new method to coat a-TiO₂-NH₂ NPs with BSA (a-TiO₂-NH₂/BSA) was proposed, allowing for a high dispersion and colloidal stability in a cell culture media. The a-TiO₂-NH₂/BSA NPs showed no cancer cell cytotoxicity. In a second step, the use of shock waves to stimulate a-TiO₂-NH₂/BSA NPs, was evaluated and optimized. A systematic study was performed in in vitro cell culture aiming to impair the cancer cell viability: NP concentrations, time steps and single versus multiple shock waves treatments were studied. The obtained results highlighted the relevance of NPs design and administration time point with respect to the shock wave treatment and allow to hypothesize mechanical damages to cells.

Recent advances in nanomedicine toward cancer treatment have considered exploiting liposomes and extracellular vesicles as effective cargos to deliver therapeutic agents to tumor cells. Meanwhile, solid-state nanoparticles are continuing to attract interest for their great medical potential thanks to their countless properties and possible applications. However, possible drawbacks arising from the use of nanoparticles in nanomedicine, such as the nonspecific uptake of these materials in healthy organs, their aggregation in biological environments and their possible immunogenicity, must be taken into account. Considering these limitations and the intrinsic capability of phospholipidic bilayers to act as a biocompatible shield, their exploitation for effectively encasing solid-state nanoparticles seems a promising strategy to broaden the frontiers of cancer nanomedicine, also providing the possibility to engineer the lipid bilayers to further enhance the therapeutic potential of such nanotools. This work aims to give a comprehensive overview of the latest developments in the use of artificial liposomes and naturally derived extracellular vesicles for the coating of solid-state nanoparticles for cancer treatment, starting from in vitro works until the up-to-date advances and current limitations of these nanopharmaceutics in clinical applications, passing through in vivo and 3D cultures studies.

The implementation of drug delivery systems in nanomedicine aims to improve the efficacy, safety and stability of therapeutic substances within the body, while controlling their rate and time of release. While numerous reviews over the years have thoroughly summarized the most recent advances and applications of drug delivery systems, to the best of our knowledge none has ever approached the topic by focusing on the impact of their structural order on both drug loading and the resulting therapeutic outcome. In this review, we aim to highlight the importance of considering the intrinsic properties of the carriers in terms of atomic, molecular and supramolecular order. Indeed, each level of order enables specific interactions between the carrier and cargo, leading to unique properties of the resulting nanosystems. Depending on the final application, the choice of a specific drug delivery system can therefore significantly influence the therapeutic effects. Thus, our work aims to facilitate the design of drug delivery systems by elucidating which level of intrinsic material order is most appropriate for a given clinical challenge. The literature search included PubMed and Scopus covering the period from January 2000 to July 2025.