PURPOSE: A novel paclitaxel delivery system has the potential to avoid the side effects associated with Cremophor EL and thus enhance therapeutic efficacy. Here, we report the results of a preclinical and phase I clinical study investigating ZSYY001, a nanoparticle formulation of polymeric micellar paclitaxel (PM-paclitaxel). METHODS: In preclinical studies, A549, MDA-MB-231, and SKOV3 xenograft tumor models were developed. Various concentrations of ZSYY001 were administered, and tumor growth and body weight were measured. Sprague-Dawley (SD) rats and Beagle dogs were used to evaluate the toxicity. In the phase I study, a dose-escalation study using a 3 + 3 design was conducted in patients with solid tumors. The PM-paclitaxel dose was escalated from 175 mg/m to 390 mg/m. PM-paclitaxel was intravenously administered over 3 h every 21 days without any premedication. This study was registered with number CTR20210347. RESULTS: Preclinical studies showed that ZSYY001 significantly inhibited tumor growth without causing weight loss. In the phase I study, all patients were evaluable for toxicity and pharmacokinetic analysis, and 18 patients were evaluable for tumor response. Acute hypersensitivity reactions were not observed. Anemia and hair loss were the most common toxicities. Dose-limiting toxicity events were not observed at any dose levels. Dose escalation to 390 mg/m did not identify a maximum-tolerated dose. There were two partial responses (11.11%) and seven cases of stable disease (38.89%) among the 18 patients, five of whom had prior exposure to paclitaxel chemotherapy. The paclitaxel area under the curve and peak paclitaxel concentration suggest that PM-paclitaxel does not exhibit linear pharmacokinetics. CONCLUSIONS: ZSYY001 was safe and well tolerated without additional toxicity and exhibited desirable antitumor activity, making it a promising treatment. TRIAL REGISTRATION: CTR20210347.