研究与开发杂志

研究与开发杂志
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国际标准期刊号: 2311-3278

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纳米医学 2017:体外和体内药物输送的抗癌治疗诊断方法

苏布拉·莫哈帕特拉

过去十年,抗癌药物递送方法取得了重大进展,尽管存在许多挑战,包括有限的纳米和生物材料的可用性、内体吸收和释放药物、将药物靶向所需的患病细胞或组织,以及缺乏研究药物输送的可转化模型。为了应对这些挑战,我们开发并测试了许多新颖的药物输送方法。为此,我们首先开发了一种近红外(NIR)触发的药物递送平台,该平台基于壳聚糖改性的化学还原氧化石墨烯(CRGO)并掺入热敏纳米凝胶(CGN)中。CGN 表现出与 CRGO 相似的近红外诱导热效应、37-42°C 下的可逆热响应特性以及高盐酸阿霉素 (DOX) 负载能力 (48 wt%)。负载 DOX 的纳米凝胶在 42 °C 时释放 DOX 的速度比在 37 °C 时更快。其次,由于化疗与基因治疗相结合是最有前途的癌症治疗策略之一,因此我们开发了一种壳聚糖功能化磁性石墨烯(CMG)纳米颗粒平台,用于同时将基因/药物和 SPIO 递送至肿瘤。这些研究结果表明,CMG 提供了一个坚固且安全的治疗诊断平台,该平台集成了基因治疗和化疗药物的靶向运输以及更有利的肿瘤 MR 成像。此外,考虑到主要用于 T1 MR 成像的钆 (Gd) 造影剂具有过量的毒性和可能的​​副作用以及肾源性系统性纤维化,我们开发了一种选择 T1 造影剂,例如用于肺部成像的锰。在这里,我们记录了用于 MRI 的含有氧化锰 (M-LMN) 的多功能脂质胶束纳米粒子 (LMN) 的图表和合成,也可用于 DNA 和药物输送。最后,我们开发了一种肿瘤样培养平台的体外模型,用于测试药物向肿瘤的递送,该平台仔细模拟体内肿瘤。总的来说,这些进展预计将导致更好的抗癌药物递送以对抗癌症。

目前的诊断策略希望扩大到提供预先检测能力,而常规的癌症治疗化疗方法由于缺乏特异性和全身毒性而受到限制。该评估强调了纳米技术的进步,这些进步使得大多数癌症检测、治疗和监测的多功能平台得以开发。纳米材料可用作MRI、光学成像和光声成像的区分剂。当用作药物载体时,纳米制剂可以将肿瘤宣传扩大到治疗经销商,并通过延长循环时间、防止包埋的胶囊降解、通过 EPR 效应以及受体介导的内吞作用改善肿瘤摄取,最终提高治疗效果。多种治疗营销商,例如化疗、抗血管生成或基因治疗药物可以同时通过纳米载体递送到肿瘤网站以增强治疗效果。此外,影像和治疗经销商可以共同提供诊断、治疗和随访的无缝集成,并且可以共同施用化疗和热疗等特殊治疗方式以获得协同效应。脂质体、钢纳米粒子、聚合物纳米粒子、树枝状聚合物、碳纳米管和量子点是可用作癌症治疗诊断学多功能系统的纳米制剂的例子。癌症纳米医学方法在临床转化方面具有巨大的潜力,可以对平均诊断和治疗过程产生积极影响,并最终为癌症患者带来更好的最佳生活方式。然而,为了彻底发现人类安全使用的长期风险、影响和预防措施,协调一致的科学努力仍然是不可或缺的。

Liposomes are concentric, closed bilayer membranes of water insoluble polar lipids that can be used to encapsulate biomolecules and tablets for centered delivery while protecting their bioactivity. Liposomal DOX has been investigated clinically for breast cancer, ovarian cancer, AIDS-related Kaposi’s sarcoma, head/neck cancer, and intelligence tumors. A approach to overcome these limitations by way of decorating the surface of the nanoparticles with focused on moieties such as small ligands, antibodies, or biomarkers that can direct the delivery car toward precise molecular aims which are overexpressed through tumor cells. Targeted particles can then be internalized with the aid of tumor cells by means of receptor-mediated endocytosis/phagocytosis, resulting in extended concentrations in tumor tissue.

Although antibodies can be at once conjugated to capsules except the use of a vehicle, scientific trials have highlighted the difficulties of applying this approach, on the whole due to possible loss of bioactivity upon conjugation, steric hindrance, and immunogenicity of the antibodies when used in their full form. In contrast, conjugating antibodies to the floor of a shipping vehicle does no longer interfere with the bioactivity or traits of the entrapped drug, and does no longer result in loss of affinity of the antibody for the target, which makes nanocarriers an fantastic platform for the improvement of nice targeted therapies. The purposes of antibodies in centered treatment options have evolved toward the preferential use of monoclonal antibodies (mAbs), especially making an attempt to avoid or reduce immunogenicity by using using engineered chimeric or humanized types to maximize the chances of successful medical translation.

Different nanocarriers have been investigated for topical/dermal transport of drugs. This part will talk about the most regularly used, topically applied carriers for the cure of pores and skin cancer. Topical nanocarriers ought to enhance skin targeting, enhancing the drug’s capability to reach and penetrate into tumor cells. Moreover, nanocarriers can improve drug steadiness and limit skin irritation by way of heading off direct contact of the drug with the skin’s surface. Different nanocarriers have been used for topical application. Present investigations emphasize theories and complete explorations about lipid-based nanocarriers, polymer-based nanocarriers, nano emulsions, and nanogels for skin most cancers treatment. They were characterized for in vitro checking out such as surface morphology, particle dimension distribution, zeta potential, pH value, viscosity, drug content, entrapment efficiency, pores and skin permeation studies, pores and skin retention/deposition studies, ex vivo vesicle-skin interplay studies, in vitro anticancer activity, , spread ability, and in vitro stability studies. Several research focus on in vivo anticancer research in 7,12-dimethylbenz[a]-anthracene (DMBA) mice model, xenografts model, and biodistribution and pharmacokinetic studies. In future, more attentiveness should be concentrated on pores and skin stimulation, skin irritation, sensitization studies, organ toxicity, and systemic toxicity of the topical nanocarriers containing anticancer drug. The universal purpose is to discover the tactics for administration of skin most cancers by way of novel methodology instead of growing novel lively moiety.

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