Background <p>Nanomedicine education requires interdisciplinary integration that conventional didactic instruction inadequately develops, particularly in glioma therapeutics. Open science practices and feedback-based pedagogy offer complementary solutions, yet their synergistic effects remain empirically unexplored. This study aimed to validate an integrated instructional framework to enhance knowledge mastery and innovation capacity.</p> Methods <p>A two-arm parallel-group randomized controlled trial was conducted at six Chinese medical colleges from October to December 2023. Three hundred forty-two clinical medicine graduate students were randomly assigned to either an experimental group (feedback-based pedagogy combined with open science platform engagement, sample size 171) or a control group (traditional didactic instruction, sample size 171) for 12 weeks. Knowledge mastery was measured using a 20-item standardized test (range 0-140), and innovation capacity was assessed using an adapted 28-item Abbreviated Torrance Test for Adults. A moderated mediation model with bootstrap resampling (5000 iterations) examined the mediating role of knowledge mastery and the moderating role of open science engagement.</p> Results <p>Feedback-based pedagogy significantly improved knowledge mastery (standardized coefficient = 0.28, <i>p</i> &lt; 0.001) and innovation capacity. Open science practice significantly amplified these effects, with a positive interaction between the two strategies (standardized coefficient = 0.15, <i>p</i> = 0.003). Knowledge mastery mediated 38.2% of the effect of feedback-based pedagogy on innovation capacity. Open science engagement significantly moderated this indirect pathway, amplifying the mediated effect by 58% under high-engagement conditions. Subgroup analyses confirmed the stability of these effects across institutional tiers and specialties. Additional objective artifact scoring showed higher blinded behavioral-output scores in the experimental group across decision quality, design feasibility, reproducible protocol/code quality, and translational rationale. Leave-one-institution-out validation confirmed that the main effect, interaction effect, and conditional indirect pathway remained directionally stable across all six institutional exclusions.</p> Conclusions <p>Integrating open science practices with feedback-based pedagogy creates a synergistic instructional paradigm that enhances nanomedicine education outcomes. Knowledge mastery serves as the critical transformation mechanism linking structured instruction to innovative capacity development. These findings provide an empirically grounded framework for glioma therapeutics education, with hypothesized applicability to other complex medical domains sharing specified boundary conditions (high interdisciplinary integration, open digital infrastructure, and simulation-based learning contexts). Boundary statement: Because this randomized trial was conducted over 12 weeks within a single national educational system and used proximal simulated/domain-adapted innovation assessments rather than downstream clinical behavioral outcomes, the findings should be interpreted as bounded evidence requiring longitudinal, cross-national replication with objective endpoints such as supervised clinical practice records, decision-quality ratings, peer-reviewed outputs, protocol contributions, and patent applications.</p>