{"doi":"10.3389/fceng.2022.997607","title":"Enzyme-responsive polymersomes ameliorate autophagic failure in a cellular model of GM1 gangliosidosis","abstract":"GM1 gangliosidosis is a lysosomal storage disorder caused by deficiency of β-galactosidase (βgal) and subsequent accumulation of GM1 ganglioside in lysosomes. One of the pathological aspects of GM1 gangliosidosis, and other storage disorders, is impaired autophagy, i.e., a reduced fusion of autophagosomes and lysosomes to degrade cellular waste. Enzyme replacement therapy (ERT) can effectively treat systemic deficiency but is limited by immunogenicity and shortened half-life of intravenously administered enzyme. In this paper, we report a hyaluronic acid- b -polylactic acid (HA-PLA) polymersome delivery system that can achieve an enzyme-responsive and sustained delivery of βgal to promote the cell’s self-healing process of autophagy. HA-PLA polymersomes have an average diameter of 138.0 ± 17.6 nm and encapsulate βgal with an efficiency of 77.7 ± 3.4%. In the presence of model enzyme Hyaluronidase, HA-PLA polymersomes demonstrate a two-fold higher release of encapsulant than without enzyme. We also identified reduced autophagy in a cellular model of GM1 Gangliosidosis (GM1SV3) compared to healthy cells, illustrated using immunofluorescence. Enhanced autophagy was reported in GM1SV3 cells treated with βgal-loaded polymersomes. Most notably, the fusion of lysosomes and autophagosomes in GM1SV3 cells returned to normal levels of healthy cells after 24 h of polymersome treatment. The HA-PLA polymersomes described here can provide a promising delivery system to treat GM1 Gangliosidosis.","journal":"Frontiers in Chemical Engineering","year":2022,"id":261405,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":560928,"name":"Sarah E. Smith","orcid":"0000-0003-1570-5700","position":1,"is_corresponding":false},{"id":576884,"name":"Jessica Larsen","orcid":"0000-0003-2756-9523","position":2,"is_corresponding":false},{"id":915732,"name":"Bipin Chakravarthy Paruchuri","orcid":"0000-0001-7285-023X","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T00:26:12.158801Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}