Rocha Vânia, Almeida Helena, Sarmento Bruno, das Neves José
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Pharmaceutics. 2025 Apr 2;17(4):460. doi: 10.3390/pharmaceutics17040460.
Candidiasis remains a chief concern in global healthcare. Drug safety issues and increasing resistance make it urgent to develop alternative antifungal agents, namely antimicrobial peptides. Amidated decoralin (Dec-CONH) possesses considerable anti- activity, and its association with nanocarriers could help in enhancing efficacy while reducing intrinsic toxicity to the host. We studied an -terminal cysteine-modified version of the peptide (Cys-Dec-CONH) and screened the effects of different nanosystems (polymeric nanoparticles (NPs), liposomes and gold NPs) on its activity against azole-sensitive and azole-resistant species using a clinically relevant in vitro assay. The antifungal activity of Cys-Dec-CONH was maintained (minimum inhibitory concentration (MIC) = 16-64 µg/mL), but the presence of poly(d,l-lactic-co-glycolic acid) (PLGA)- and polycaprolactone-based NPs impaired the antifungal effect of the peptide (MIC > 256 µg/mL). This effect was milder for polystyrene-based NPs, liposomes, and gold NPs (MIC ≤ 128 µg/mL). Additionally, the covalent surface functionalization of PLGA-based NPs with Cys-Dec-CONH or the presence of relevant biomolecules (albumin and mucin) resulted in complete inhibition of antifungal activity. Our data suggest that Cys-Dec-CONH is able to establish strong interfacial interactions with different nanomaterials, which need to be considered when developing nanomedicines based on this peptide for the management of candidiasis.
念珠菌病仍然是全球医疗保健中的一个主要问题。药物安全问题和耐药性增加使得开发替代抗真菌剂（即抗菌肽）变得紧迫。酰胺化的德卡林（Dec-CONH）具有相当的抗活性，并且它与纳米载体的结合有助于提高疗效，同时降低对宿主的内在毒性。我们研究了该肽的N端半胱氨酸修饰版本（Cys-Dec-CONH），并使用临床相关的体外试验筛选了不同纳米系统（聚合物纳米颗粒（NPs）、脂质体和金纳米颗粒）对其针对唑类敏感和唑类耐药菌株的活性的影响。Cys-Dec-CONH的抗真菌活性得以维持（最低抑菌浓度（MIC）=16-64μg/mL），但聚（d，l-乳酸-共-乙醇酸）（PLGA）和聚己内酯基纳米颗粒的存在损害了该肽的抗真菌作用（MIC>256μg/mL）。对于聚苯乙烯基纳米颗粒、脂质体和金纳米颗粒，这种影响较轻微（MIC≤128μg/mL）。此外，用Cys-Dec-CONH对PLGA基纳米颗粒进行共价表面功能化或存在相关生物分子（白蛋白和粘蛋白）会导致抗真菌活性完全受到抑制。我们的数据表明，Cys-Dec-CONH能够与不同的纳米材料建立强烈的界面相互作用，在开发基于该肽的纳米药物用于念珠菌病的治疗时需要考虑这一点。
