Additional file 1: of Co-delivery of sorafenib and metapristone encapsulated by CXCR4-targeted PLGA-PEG nanoparticles overcomes hepatocellular carcinoma resistance to sorafenib

Figure S1. CXCR4 expression in HCC cell lines. (DOCX 109 kb

Additional file 3: of Co-delivery of sorafenib and metapristone encapsulated by CXCR4-targeted PLGA-PEG nanoparticles overcomes hepatocellular carcinoma resistance to sorafenib

Figure S3.1H NMR spectra of PLGA-PEG-COOH copolymer. (DOCX 93 kb

Additional file 2: of Co-delivery of sorafenib and metapristone encapsulated by CXCR4-targeted PLGA-PEG nanoparticles overcomes hepatocellular carcinoma resistance to sorafenib

Figure S2. CI values of combination treatment of sorafenib with metapristone. (DOCX 216 kb

Additional file 1 of Egfr signaling promotes juvenile hormone biosynthesis in the German cockroach

Additional file 1: Figure S1. Effect of RNAi each Egf ligand gene on Jhamt and Cyp15A1 expression. Figure S2. Effect of RNAi pairwise combinations of the three Egf ligand genes Jhamt and Cyp15A1 expression. Figure S3. Expression patterns of Egfr, spi, vn, Jhamt and Cyp15A1 of adult females, during the first vitellogenic cycle. Figure S4. Compare Egfr RNAi with InR RNAi. Figure S5. RNAi Egfr at the nymph stage. Figure S6. Egf ligands and Pnt RNAi at the nymph stage. Figure S7. Specificity verification of anti-JHAMT. Table S1. Primers used for qPCR, RNAi and 5′-RACE

Additional file 2 of Egfr signaling promotes juvenile hormone biosynthesis in the German cockroach

Additional file 2. The individual data values for Fig. 1A-C, Fig. 2A, C, D’, E’- E”, F, G’-G”, I, J, Fig. 3, A, B-B’, C-C”, D’, E’, F’-F”, G, H’-H”, J, K, Fig. 4A’-B’, C-E, F’, Fig. 5A-A”, B, C’, D’, E’, F, G’, H’, Fig. 6B-C, D-D”, E, Fig. S1A-A”, B-B”, C-C”, D’-F’, Fig. S2A-A’, B-B’, C’-D’, Fig. S3A-D, Fig. S4B-E, Fig. S5B-E and Fig. S6B-C

Additional file 3 of Egfr signaling promotes juvenile hormone biosynthesis in the German cockroach

Additional file 3. Original Western blot data

Dual Enzyme Cascade-Activated Popcorn-Like Nanoparticles Efficiently Remodeled Stellate Cells to Alleviate Pancreatic Desmoplasia

In pancreatic cancer, excessive desmoplastic stroma severely impedes drug access to tumor cells. By reverting activated pancreatic stellate cells (PSCs) to quiescence, all-trans retinoic acid (ATRA) can attenuate their stromal synthesis and remodel the tumor-promoting microenvironment. However, its modulatory effects have been greatly weakened due to its limited delivery to PSCs. Therefore, we constructed a tripeptide RFC-modified gelatin/oleic acid nanoparticle (RNP@ATRA), which delivered ATRA in an enzyme-triggered popcorn-like manner and effectively resolved the delivery challenges. Specifically, surface RFC was cleaved by aminopeptidase N (APN) on the tumor endothelium to liberate l-arginine, generating nitric oxide (NO) for tumor-specific vasodilation. Then, massive nanoparticles were pushed from the vessels into tumors, showing 5.1- and 4.0-fold higher intratumoral accumulation than free ATRA and APN-inert nanoparticles, respectively. Subsequently, in the interstitium, matrix metalloproteinase-2-induced gelatin degradation caused RNP@ATRA to rapidly release ATRA, promoting its interstitial penetration and PSC delivery. Thus, activated PSCs were efficiently reverted to quiescence, and stroma secretion and vascular compression were reduced, thereby enhancing intratumoral delivery of small-molecule or nanosized chemotherapeutics. Ultimately, RNP@ATRA combined with chemotherapeutics markedly suppressed tumor growth and metastasis without causing additional toxicities. Overall, this work provides a potential nanoplatform for the efficient delivery of PSC-modifying agents in pancreatic cancer and other stroma-rich tumors

Cholinergic Neuron Targeting Nanosystem Delivering Hybrid Peptide for Combinatorial Mitochondrial Therapy in Alzheimer’s Disease

Mitochondrial dysfunction in neurons has recently become a promising therapeutic target for Alzheimer’s disease (AD). Regulation of dysfunctional mitochondria through multiple pathways rather than antioxidation monotherapy indicates synergistic therapeutic effects. Therefore, we developed a multifunctional hybrid peptide HNSS composed of antioxidant peptide SS31 and neuroprotective peptide S14G-Humanin. However, suitable peptide delivery systems with excellent loading capacity and effective at-site delivery are still absent. Herein, the nanoparticles made of citraconylation-modified poly­(ethylene glycol)-poly­(trimethylene carbonate) polymer (PEG-PTMC­(Cit)) exhibited desirable loading of HNSS peptide through electrostatic interactions. Meanwhile, based on fibroblast growth factor receptor 1­(FGFR1) overexpression in both the blood–brain barrier and cholinergic neuron, an FGFR1 ligand-FGL peptide was modified on the nanosystem (FGL-NP­(Cit)/HNSS) to achieve 4.8-fold enhanced accumulation in brain with preferred distribution into cholinergic neurons in the diseased region. The acid-sensitive property of the nanosystem facilitated lysosomal escape and intracellular drug release by charge switching, resulting in HNSS enrichment in mitochondria through directing of the SS31 part. FGL-NP­(Cit)/HNSS effectively rescued mitochondria dysfunction via the PGC-1α and STAT3 pathways, inhibited Aβ deposition and tau hyperphosphorylation, and ameliorated memory defects and cholinergic neuronal damage in 3xTg-AD mice. The work provides a potential platform for targeted cationic peptide delivery, harboring utility for peptide therapy in other neurodegenerative diseases