Photodynamic therapy (PDT), as a non-invasive treatment, has received wide attention because of its high selectivity and low side effects. However, traditional PDT is influenced by the excitation light source and the light penetration depth is limited, which can only be used for superficial epidermal tumor treatment, and it is still a great challenge for deep tumor treatment. In recent years, X-ray excitation photodynamic therapy (X-PDT) using penetrating X-rays as an external excitation source and X-ray excited luminescent nanoparticles (XLNP) as an energy transfer medium to indirectly excite photosensitizer (PS) has solved the problem of insufficient penetration depth in tissues and become a research hotspot in the field of deep tumor treatment. In this review, the recent research progress of nanoparticles for efficient X-PDT, listing different types of XLNP and luminescence enhancement strategies. The loading method of PS is highlighted to achieve efficient energy transfer by regulating the intermolecular distance between both XLNP/PS. In addition, the water-soluble modification of XLNP surface is discussed and different hydrophilic modification methods are proposed to provide reference ideas for improving the dispersibility and biocompatibility of XLNP in aqueous solution. Finally, the therapeutic effects about X-PDT are discussed, and the current challenges and future perspectives for its clinical applications are presented.
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