Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in clinical practice, primarily caused by abnormal overactivation of the Hedgehog signaling pathway. However, currently available small molecule target inhibitors often face severe resistance bottlenecks due to triggering second-generation mutations in the SMO protein. This study pioneeringly integrates artificial intelligence (AI) medical computing, natural drug development, and glycobiology in depth, systematically elucidating the precise molecular control mechanism of Chlorella lectin topical formulations for human BCC, and overcoming the barrier to transdermal absorption of large molecule proteins. First, the AlphaFold3 algorithm was used to precisely predict the tertiary monomer structure of chlorella lectin, identifying a carbohydrate recognition domain (CRD) composed of core residues such as Asp54, Asn78, and Trp102. Using the DeepConv-DTI deep learning network and MM/PBSA molecular dynamics thermodynamic simulations, it was confirmed that this lectin can highly specifically target abnormal oligosaccharides overexpressed on human BCC cell membranes with extremely high affinity (\Delta G_{\text{bind}} = -

42.35\\text{kcal/mol}) 2. It is non-cytotoxic to normal human keratinocytes (HaCaT), demonstrating excellent tumor selectivity. In vitro molecular mechanism validation shows that chlorella lectin exerts a clear "dual-track" direct anti-cancer molecular mechanism against human BCC cells: it blocks oncogenic pathways, such as significantly downlowering the expression of the key protein SMO in the Hedgehog signaling pathway by 55%, and effectively blocking nuclear translocation of transcription factors GLI1/GLI2 (reducing downstream target gene transcription by 62%), thereby suppressing uncontrolled tumor cell proliferation and invasion at the source. This leads to the restart of endogenous apoptosis: it induces a significant reversal between the pro-apoptotic protein Bax and anti- apoptotic protein Bcl-2 (upregulated by 3.5 times, and by 70% downward), leading to changes in mitochondrial outer membrane permeability and cytochrome c release, which in turn cascades activation of Caspase-9 and Caspase-3 (activation increased by 4.2 times), driving BCC cells toward programmed death. Furthermore, to address the clinical pain point where large molecule proteins struggle to penetrate the stratum corneum, this study introduced Bayesian Optimization algorithms for global prescription screening. With just 18 intelligent iterations, an optimized nanolipid carrier (LNP) with an average particle size of 118.6\\text{nm} and an encapsulation rate of 89.4% was successfully developed. Franz diffusion cell experiments confirmed that this optimized formulation increased transdermal cumulative penetration by 4.8 times, stabilizing local drug concentrations at lesions above \text{IC}_{50} (28.4\ \mu\text{g/mL}), successfully achieving efficient, non-invasive local targeted delivery.

In summary, this study not only confirms that Chlorella lectin is a novel green macromolecule anti-skin cancer agent with high selectivity and low resistance risk, but also successfully builds a full-chain AI medical platform combining "prediction - simulation - intelligent formulation", paving the way for future natural product targeted drug development and clinical precision medicine translation; It has established an innovative scientific milestone and made outstanding contributions in cell biomedicine.