UCPs/Zn2GeO4:Mn2+/g-C3N4 heterojunction engineered injectable thermosensitive hydrogel for oxygen independent breast cancer neoadjuvant photodynamic therapy

Neoadjuvant chemotherapy for the treatment of breast cancer can provide the option of surgery for patients with a large tumor mass or increase the rate of breast conservation. However, some patients are not sensitive to chemotherapeutic drugs, and therefore this may cause them to miss their optimal chance for surgery. Herein, photodynamic therapy (PDT) was chosen instead of chemotherapy as a neoadjuvant treatment for breast cancer because of its effectiveness against different cancer cells and the lack of side effects in normal tissues. Considering the hypoxic environment of tumors and the tissue penetration depth, a heterojunction Zn₂GeO₄:Mn²⁺/g-C₃N₄ was designed and combined with upconversion materials NaYF₄:Yb³⁺, Tm³⁺ and hyaluronic acid to form a NaYF₄:Yb³⁺, Tm³⁺/Zn₂GeO₄:Mn²⁺/g-C₃N₄@HA (UZC@HA) photosensitizer. After intratumoral administration using a thermosensitive hydrogel as a carrier, under a 980 nm laser, UZC@HA can generate holes and electrons to oxidize water to form a hydroxyl radical (˙OH) and react with O₂ to produce the superoxide ion (˙O₂^-), respectively. The thermosensitive hydrogel not only supplies water, but also ensures the high loading capacity of UZC@HA. HA on the UZC can bind specifically with CD44R-overexpressing tumor cells and help the photosensitizer to target tumor sites. Thus, near infrared (NIR) mediated oxygen-independent PDT can be realized. After 12 d of treatment, the tumor mass was significantly reduced and no side effects in normal tissues were observed. Our work shows the potential of the NIR mediated heterojunction UZC@HA to act as a photosensitizer for neoadjuvant PDT in breast cancer and may open a new avenue for exploration of PDT and provide more options for breast cancer patients.