Pacheco Ana Rita F, Cardoso Beatriz D, Pires Ana, Pereira André M, Araújo João P, Carvalho Violeta M, Rodrigues Raquel O, Coutinho Paulo J G, Castelo-Grande Teresa, Augusto Paulo A, Barbosa Domingos, Lima Rui A, Teixeira Senhorinha F C F, Rodrigues Ana Rita O, Castanheira Elisabete M S
Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Associate Laboratory LaPMET, 4710-057 Braga, Portugal.
Nanomaterials (Basel). 2023 Mar 15;13(6):1051. doi: 10.3390/nano13061051.
Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (MgCaFeO) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The MgCaFeO calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.
传统治疗方法所带来的诊断延迟和全身毒性使得肿瘤治疗极具难度。在此背景下，纳米医学作为癌症预防、诊断和治疗的一种新方法应运而生。在本研究中，开发了pH敏感型固体磁脂质体（SMLs）用于化疗药物阿霉素（DOX）的控释。合成了部分被钙取代的镁铁氧体形状各向异性磁性纳米颗粒（MgCaFeO），有煅烧和未煅烧两种情况，并对其结构、形态和磁性进行了研究。通过暴露于交变磁场（AMF）（磁热疗）或近红外（NIR）光照射（光热疗）评估了它们的超顺磁性特性并证明了其加热能力。选择煅烧后的MgCaFeO纳米颗粒来构建SMLs，其被DOPE:Ch:CHEMS（45:45:10）的脂质双层包围。DOX被封装在纳米系统中，封装效率高于98%。DOX释放试验表明，与生理pH下的释放动力学相比，在pH = 5时药物释放效率更高。通过将肿瘤细胞暴露于负载DOX的SMLs中，细胞活力显著降低，证实它们能够释放封装的药物。这些结果表明开发出了高效的pH敏感型纳米载体，适用于在癌症治疗中通过磁靶向、刺激控制药物递送和双热疗（磁热疗和等离子体热疗）发挥协同作用。
