This study evaluated the effects of the incorporation of copaiba essential oil in corn starch in encapsulated and direct forms in films formulated with poly(vinyl alcohol), polyvinylpyrrolidone, and propylene glycol. The characterization of the essential oil, performed via gas chromatography coupled to mass spectrometry, identified beta-caryophyllene as the main sesquiterpene. From the oil, a nanoemulsion was developed that, after spray drying, provided the microparticles used in the production of films using the casting technique. The encapsulated copaiba essential oil (CEO) showed an encapsulation efficiency (%) of 76.12% +/- 0.15. Thermogravimetric analysis revealed that the encapsulated CEO microparticles showed higher thermal stability than free essential oil, preserving the structural integrity of their compounds even at high temperatures. The F3 film containing encapsulated CEO presented the lowest thickness (0.48 +/- 0.05) and the lowest moisture content (16.07 +/- 0.06) compared to the F2 film with CEO in the nonencapsulated form and the F1 control film, evidencing a more stable interaction between the encapsulated oil and the starch matrix. The hydration capacity of F3 was positioned between those observed in the F1 and F2 films, suggesting that the encapsulation technique improved the structural compatibility and improved water retention over time. The F1 film presented a tensile strength of 5.15 MPa, while the F3 and F2 films presented slightly higher values of 5.41 and 5.33 MPa, respectively. The modulus of elasticity of F1 was 1.40 MPa. In comparison, F2 showed a decrease, registering 1.28 MPa, which indicates greater flexibility, and F3 showed a slight increase, reaching 1.45 MPa, suggesting a relatively greater rigidity. The F3 film indicated a significant increase in elongation, reaching 41.79%, compared to F1's 27.07% and F2's 28.74%. These results suggest that encapsulation improved the ductility and mobility of the polymer chains, demonstrating the best balance between strength, rigidity and flexibility compared to the F1 and F2 films. In the FTIR spectra, it was evident that the addition of the encapsulated CEO affected the chemical structure of the film, as it demonstrated changes in the bands of the region 1750-1000 cm-1, revealing that there were different interactions of the oil with the polymer matrix. These findings reinforce the promising use of encapsulated CEO in pharmaceuticals, healthcare, and biodegradable packaging.
The immunosuppressive microenvironment of osteosarcoma (OS) and the inherent toxicity of current neoadjuvant chemotherapy present significant challenges in treatment, highlighting the urgent need for innovative therapeutic approaches. Photodynamic therapy (PDT) is a promising noninvasive alternative; however, its clinical application is limited by the poor stability of traditional photosensitizers (PS), insufficient reactive oxygen species (ROS) production, and a weak antitumor immune response. Given these limitations, a combination therapy that enhances PDT's therapeutic efficacy while stimulating immune activation could offer a more effective strategy. In this study, we developed a biomimetic nanomedicine (IR780@EM) by integrating the near-infrared photosensitizer IR780 with Escherichia coli-derived membrane nanovesicles (EM). This approach synergistically combines localized PDT with systemic antitumor immunity, leading to enhanced ROS generation and promoting M2-to-M1 polarization of macrophages in tumor, thereby activating the immune system and driving OS regression. Unlike conventional chemotherapy-based treatments, this strategy not only addresses the key limitations of PDT-insufficient ROS production and limited immune activation-but also helps overcome chemotherapy resistance and convert immunologically "cold" tumors into "hot" tumors, thereby improving therapeutic outcomes. This EM-based nanotherapeutic strategy holds significant translational potential for optimizing PDT efficacy and offers a multidimensional treatment approach for OS.
Biotechnology and biomedical advances have driven the development of novel biopharmaceuticals to meet growing clinical demands. Among approved biologics, native Escherichia coli asparaginase has been under continuous optimization to improve thermostability, half-life, resistance to human proteases, and reduce adverse effects, particularly allergenicity. Here, we engineered an antileukemic biobetter by combining the substitutions P40S/S206Cpreviously identified by our group as less immunogenic and with extended bloodstream activity in micewith N24S, reported to enhance in vitro stability. The purified triple mutant enzyme was biochemically characterized, and its cytotoxicity against leukemic cell lines and antigenic properties in Balb/c SPF mice were evaluated. TM displayed robust asparaginase activity, a >3-fold reduction in K M for asparagine, superior thermostability, enhanced proteolytic resistance, and a lower in silico immunogenicity score compared to wild-type. In vivo, compared to wild-type, TM showed no apparent toxicity, a lower decrease in platelet counts, reduced induction of antiasparaginase IgE antibodies, and a preserved pharmacokinetic profile. In conclusion, combined mutations conferred substantial biochemical and immunological improvements, supporting the strategy of targeted amino acid substitutions to advance next-generation asparaginase biopharmaceuticals.
T-cell acute lymphoblastic leukemia (T-ALL) is an invasive hematological malignancy characterized by a high relapse rate, due to the lack of targeted therapies. Despite intensive chemotherapy having advanced treatment progress, most patients experience treatment failure and endure severe side effects. Here, a CD7-specific polymersomal vincristine delivery system was engineered on the basis of anti-CD7 nanobody-conjugated chimeric polymersomes (aCD7P-VCR) for targeted chemotherapy of T-ALL. aCD7P-VCR, with tunable aCD7 nanobody density, mediated selective targeting and potent inhibition of CD7-positive CCRF-CEM T-ALL cells, resulting in a half-maximal inhibitory concentration of 0.11 nM VCR, but caused no obvious toxicity to normal peripheral blood mononuclear cells or T cells at 10.8 nM VCR. Interestingly, aCD7P-VCR treatment substantially reduced leukemia progression and invasion in the orthotopic CCRF-CEM T-ALL model without toxic effects, leading to significantly longer survival than clinically used VCR and nontargeted P-VCR. aCD7P-VCR is expected to provide an effective and targeted therapeutic approach for T-ALL.
