Maria Alice de Oliveira

Background: Combination chemotherapy using nanotechnology-based delivery is a promising approach to improve cancer treatment, but the added value of co-loaded polymeric nanocarriers has not been comprehensively appraised. This review synthesizes preclinical evidence on polymeric systems co-encapsulating antitumor agents. Methods: A narrative literature review identified 33 preclinical studies (2015–2025) employing polymer-based nanocarriers to co-load at least two antitumor drugs. Study characteristics and in vitro and in vivo outcomes were qualitatively analyzed. Results: Most studies addressed breast, lung, or ovarian cancer and used micelles or nanospheres. Co-loaded formulations consistently enhanced in vitro cytotoxicity and, in vivo, produced marked tumor growth inhibition relative to free drugs or single-loaded systems; in several reports, near-complete or complete tumor regression was achieved. Synergy was frequently suggested but not consistently quantified, more than half of the studies did not report a combination index. Most formulations showed favorable tolerability, with few reports including mild hepatic toxicity, renal, or weight-related effects. Beyond conventional drug pairs, examples of co-delivering chemotherapeutics with resistance modulators, gene therapy agents, or targeted ligands illustrated how tailored release profiles and active targeting can potentiate efficacy. Nevertheless, heterogeneity in models, dosing schedules, endpoints, and limited long-term safety data hamper cross-study comparison and translation. Conclusions: Co-loaded polymeric nanocarriers constitute a promising platform to optimize combination chemotherapy, improving preclinical antitumor efficacy with generally limited toxicity, but more standardized and mechanistically driven studies are required to support clinical development.

The therapeutic management of Chagas disease requires new medicines because the standard-of-care drugs available induce adverse effects and have limited efficacy. In this study, we developed a formulation of albaconazole (ABZ) loaded in biodegradable polymeric nanocapsules (NCs). Free ABZ and ABZ-loaded NCs were similarly active against the Y strain and inactive against the Colombian strain epimastigotes of Trypanosoma cruzi. Infected mice were given ABZ in different doses and treatment schedules by oral, SC, and IM routes during the acute phase of infection. Free ABZ taken orally reduced parasitemia and suppressed mortality; however, all the animals maintained patent parasitemia during and after treatment. ABZ-NCs increased anti-T. cruzi effects (p < 0.05), inducing negative parasitemia during treatment in most of the tested regimens. The parasitemia level was also significantly reduced after treatment with ABZ-NCs during the acute phase of the disease, and relapses were delayed compared with the free ABZ treatment. Once- and twice-daily doses were similarly effective, demonstrating that the NCs prolonged the ABZ-NC residence time. Free ABZ and ABZ-NCs did not prevent infection, ABZ seemed to have suppressive effects on T. cruzi growth, and encapsulation prolonged this suppression. The analysis of the in vivo results indicated that the NCs significantly improved the safety of ABZ in the mouse model, suggesting that the increased ABZ-NC dosage regimen merits further efficacy and pharmacokinetic evaluations.

Photodynamic and photothermal therapies with IR780 have gained exponential interest, and their photophysical properties have demonstrated promise for use in antitumor and antimicrobial chemotherapy. IR780 and its derivatives are valuable in labeling nanostructures with different chemical compositions for in vitro and in vivo fluorescence monitoring studies in the near-infrared (NIR) spectrum. The current literature is abundant on this topic, particularly with applications in the treatment of different types of cancer using laser illumination to produce photodynamic (PDT), photothermal (PTT), and, more recently, sonodynamic therapy (SDT) approaches for cell death. This review aims to update the state of the art concerning IR780 photosensitizer as a theranostic agent for PDT, PTT, SDT, and photoacoustic (PA) effects, and fluorescence imaging monitoring associated with different types of nanocarriers. The literature update concerns a period from 2017 to 2024, considering, more specifically, the in vivo effects found in preclinical experiments. Some aspects of the labeling stability of nanostructured systems will be discussed based on the evidence of IR780 leakage from the nanocarrier and its consequences for the reliable analysis of biological data.

Near-infrared fluorescent dyes, such as IR780, are promising theranostics, acting as photosensitizers for photodynamic therapy and in vivo tracers in image-guided diagnosis. This work compared the uptake by macrophage-like cells of IR780 either physically associated or covalently attached to poly(D,L-lactide) (PLA) formulated as polymeric nanocapsules (NC) from a blend of PLA homopolymer and PLA-PEG block copolymer. The physicochemical characterization of both NC was conducted using asymmetric flow field-flow fractionation (AF4) analysis with static and dynamic light scattering and atomic force microscopy. The interaction of IR780 with serum proteins was evidenced by AF4 with fluorescence detection and flow cytometry in cell uptake studies. The average diameters of NC were around 120 nm and zeta potentials close to -40 mV for all NC. NC uptake by cells in different media and experimental conditions shows significantly lower fluorescence intensities for IR780 covalently linked to PLA and correspondingly low quantitative uptake. Different mechanisms of internalization were evidenced depending on the IR780 type of association to NC. Serum proteins mediate IR780 interaction with cells in a dose-dependent manner. Our results show that non-covalently linked IR780 was released from NC and accumulated in macrophage cells. Oppositely, IR780 conjugated to PLA provides stable association with NC, and its fluorescence is representative of cell uptake of the nanocarrier itself. This work strongly reinforces the importance of covalent attachment of a fluorescence dye such as IR780 to the nanocarrier to study their interaction with cells in vitro and to obtain reliable tracking in image-guided therapy. Graphical abstract