Development and Characterization of Nanobody-Derived CD47 Theranostic Pairs in Solid Tumors

Overexpression of CD47 is frequently observed in various types of human malignancies,inhibiting myeloidmediated elimination of tumor cells and affecting the prognosis of cancer patients.By mapping biomarker expression,immuno-positron emission tomography has been increasingly used for patient screening and response monitoring.By immunization alpacas with recombinant human CD47,we prepared a CD47-targeting nanobody C2 and developed[^(68)Ga]Ga-NOTA-C2,followed by an exploration of the diagnostic value in CD47-expressing tumor models including gastric-cancer patient-derived xenograft models.By fusing C2 to an albumin binding domain(ABD),we synthesized ABDC2,which had increased in vivo half-life and improved targeting properties.We further labeled ABDC2 with^(68)Ga/^(89)Zr/177Lu to develop radionuclide theranostic pairs and evaluated the pharmacokinetics and theranostic efficacies of the agents in cell-and patient-derived models.Both C2 and ABDC2 specifically reacted with human CD47 with a high KD value of 23.50 and 84.57 pM,respectively.[^(68)Ga]Ga-NOTA-C2 was developed with high radiochemical purity(99>%,n=4)and visualized CD47 expression in the tumors.In comparison to the rapid renal clearance and short half-life of[^(68)Ga]Ga-NOTA-C2,both[^(68)Ga]Ga-NOTA-ABDC2 and[^(89)Zr]Zr-DFOABDC2 showed prolonged circulation and increased tumor uptake,with the highest uptake of[^(89)Zr]Zr-DFO-ABDC2 occurring at 72 h post-injection.Moreover,[177Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed the tumor growth but was associated with toxicity,warranting further optimization of the treatment schedules.Taken together,we reported a series of nanobody-derived CD47-targeted agents,of which[^(68)Ga]Ga-NOTA-C2 and[^(89)Zr]Zr-DFO-ABDC2 are readily translatable.Optimization and translation of CD47-targeted theranostic pair may provide new prospects for CD47-targeted management of solid tumors.

The combined therapeutic effects of ^(131)iodinelabeled multifunctional copper sulfide-loaded microspheres in treating breast cancer

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis.In this study, we prepared multifunctional microspheres loading ^(131)I-labeled hollow copper sulfide nanoparticles and paclitaxel( ^(131)I-HCu SNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats.18 F-fluordeoxyglucose(18 F-FDG) positron emission tomography/computed tomography(PET/CT) imaging detected that the expansion of the tumor volume was delayed(Po0.05) following intra-tumoral(i.t.) injection with ^(131)I-HCu SNPs-MS-PTX plus near-infrared(NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography(SPECT)/photoacoustic imaging mediated by ^(131)I-HCu SNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that ^(131)I-HCu SNPs-MS-PTX offered combined photothermal, chemo-and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, ^(131)I-HCu SNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.

Noncommutative Constrained KP Hierarchy and Multi-component Noncommutative Constrained KP Hierarchy

In this paper, the authors define the noncommutative constrained KadomtsevPetviashvili(KP) hierarchy and multi-component noncommutative constrained KP hierarchy. Then they give the recursion operators for the noncommutative constrained KP(NcKP) hierarchy and multi-component noncommutative constrained KP(NmcKP) hierarchy. The authors hope these studies might be useful in the study of D-brane dynamics whose noncommutative coordinates emerge from limits of the M theory and string theory.