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A similar protective effect of exogenous IL-2 was reported by Shen et al., who showed that the IL-2-treated group showed decreased sputum smear-positive rates, whereas the control group showed increased sputum smear-positive rates (218)

In addition, even although the EPR effect can facilitate the nanotherapeutic distribution to the periphery of tumors via leaky vasculatures 12,13 , efficient intracellular internalization with deep tissue penetration remains unattainable due to the formidable resistance induced by dense extracellular matrix and heightened interstitial fluid pressure on passive diffusion from the perivascular regions to the target cells and/or distal cells, compromising the therapeutic outcome 39

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Acknowledgements We thank the members of the Iwai laboratory for helpful suggestions